Oncostatic action of melatonin: facts and question marks.
The paper presents the data concerning the in vivo effects of melatonin on experimentally-induced tumors in animals and the in vitro effects on animal and human tumor cells. The majority of experimental tumors responded to the melatonin treatment with growth inhibition. However, some negative or opposite results (i.e. stimulation of tumor instead of inhibition) were also reported. Some of the negative results can be attributed to the improper timing of melatonin administration. Melatonin was also shown to inhibit the growth of several animal and human tumor cell lines in vitro. On the basis of these experiments, a hypothesis of the oncostatic action of melatonin was put forward. The mechanism of the postulated action is complex and probably includes: 1) modulation of the endocrine system; 2) modulation of the immune system; 3) the direct oncostatic action of melatonin on tumor cells. The latter includes the recently discovered anti-oxidative action which probably plays an important role in the countering the DNA damage during the radiation challenge or the exposure to chemical carcinogens. It also includes the antiproliferative and pro-apoptotic effects exerted via melatonin receptors expressed by tumor cells. The involvement of the membrane melatonin receptors is mainly assumed. However, the recent data from our and other laboratories suggest also the involvement of RZR/ROR receptors (the putative melatonin nuclear receptors) in both melatonin-induced proliferation inhibition and apoptosis.


Metabolic relationships of uncultured bacteria associated with the microalgae Gambierdiscus.
Microbial communities inhabit algae cell surfaces and produce a variety of compounds that can impact the fitness of the host. These interactions have been studied via culturing, single-gene diversity and metagenomic read survey methods that are limited by culturing biases and fragmented genetic characterizations. Higher-resolution frameworks are needed to resolve the physiological interactions within these algal-bacterial communities. Here, we infer the encoded metabolic capabilities of four uncultured bacterial genomes (reconstructed using metagenomic assembly and binning) associated with the marine dinoflagellates Gambierdiscus carolinianus and G. caribaeus. Phylogenetic analyses revealed that two of the genomes belong to the commonly algae-associated families Rhodobacteraceae and Flavobacteriaceae. The other two genomes belong to the Phycisphaeraceae and include the first algae-associated representative within the uncultured SM1A02 group. Analyses of all four genomes suggest these bacteria are facultative aerobes, with some capable of metabolizing phytoplanktonic organosulfur compounds including dimethylsulfoniopropionate and sulfated polysaccharides. These communities may biosynthesize compounds beneficial to both the algal host and other bacteria, including iron chelators, B vitamins, methionine, lycopene, squalene and polyketides. These findings have implications for marine carbon and nutrient cycling and provide a greater depth of understanding regarding the genetic potential for complex physiological interactions between microalgae and their associated bacteria.


Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion.
Novel strategies to directly thwart malaria transmission are needed to maintain the gains achieved by current control measures. Transmission-blocking interventions (TBIs), namely vaccines and drugs targeting parasite or mosquito molecules required for vector-stage parasite development, have been recognized as promising approaches for preventing malaria transmission. However, the number of TBI targets is limited and their degree of conservation among the major vector-parasite systems causing human disease is unclear. Therefore, discovery and characterization of novel proteins involved in vector-stage parasite development of Plasmodium falciparum and Plasmodium vivax is paramount. We mined the recent Anopheles gambiae midgut lipid raft proteome for putative mosquito-derived TBI targets and characterized a secreted glycoconjugate of unknown function, AgSGU. We analyzed molecular variation in this protein among a range of anopheline mosquitoes, determined its transcriptomic and proteomic profiles, and conducted both standard and direct membrane feeding assays with P. falciparum (lab/field) and P. vivax (field) in An. gambiae and Anopheles dirus. We observed that α-AgSGU antibodies significantly reduced midgut infection intensity for both lab and field isolates of P. falciparum in An. gambiae and An. dirus. However, no transmission-reducing effects were noted when comparable concentrations of antibodies were included in P. vivax-infected blood meals. Although antibodies against AgSGU exhibit transmission-reducing activity, the high antibody titer required for achieving 80% reduction in oocyst intensity precludes its consideration as a malaria mosquito-based TBI candidate. However, our results suggest that P. falciparum and P. vivax ookinetes use a different repertoire of midgut surface glycoproteins for invasion and that α-AgSGU antibodies, as well as antibodies to other mosquito-midgut microvillar surface proteins, may prove useful as tools for interrogating Plasmodium-mosquito interactions.


Organic Farming: Biodiversity Impacts Can Depend on Dispersal Characteristics and Landscape Context.
Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity.


Metabolomic signatures of aggressive prostate cancer.
Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests.


Collisional excitation of CH(X²Π) by He: new ab initio potential energy surfaces and scattering calculations.
We present a new set of potential energy surfaces (PESs) for the CH(X(2)Π)-He van der Waals system. Ab initio calculations of the CH-He PES were carried out using the open-shell single- and double-excitation coupled cluster approach with non-iterative perturbational treatment of triple excitations [RCCSD(T)]. The augmented correlation-consistent polarized valence quadruple-zeta (aug-cc-pVQZ) basis set was employed augmented by mid-bond functions. Integral cross sections for the rotational excitation in CH-He collisions were calculated using the new PES and compared with available experimental results. The newly constructed PES reproduces the available experimental results for CH(X(2)Π, v = 0)-He collisions better than any previously available PES. Differential cross sections (DCS) are presented for the first time for this system and discussed within the context of rotational rainbows. Finally, our work provides the first rate thermal coefficients for this system that are crucially needed for astrochemical modelling and future anticipated experiments in CH(X(2)Π)-He collisions.


Comparative proteomic analysis of mitochondria isolated from Euglena gracilis under aerobic and hypoxic conditions.
The unicellular microalga Euglena gracilis produces wax esters for ATP acquisition under low-oxygen conditions. The regulatory mechanism of wax ester production is not yet understood. Indeed, our previous transcriptomic analysis showed that transcript levels of genes involved in the wax ester synthesis hardly changed under hypoxic conditions, suggesting contribution of post-transcriptional regulation. In this study, we conducted a proteome analysis of E. gracilis mitochondria, as this organelle employs the fatty-acid synthesis pathway under hypoxic conditions. Mitochondria were isolated from E. gracilis SM-ZK strain treated with both aerobic and hypoxic conditions and used for shotgun proteomic analysis. Three independent proteomic analyses succeeded in identifying a total of 714 non-redundant proteins. Of these, 229 were detected in common to all experiments, and 116 were significantly recognized as differentially expressed proteins. GO enrichment analysis suggested dynamic changes in mitochondrial metabolic pathways and redox reactions under aerobic and hypoxic conditions. Protein levels of bifunctional enzymes isocitrate lyase and malate synthase in glyoxylate cycle were 1.35-fold higher under hypoxic conditions. Abundances of the propionyl-CoA synthetic enzymes, succinyl-CoA synthetase and propionyl-CoA carboxylase, were also 1.35- and 1.47-fold higher, respectively, under hypoxic conditions. Protein levels of pyruvate:NADP+ oxidoreductase, a key enzyme for anaerobic synthesis of acetyl-CoA, which serves as a C2 donor for fatty acids, showed a 1.68-fold increase under hypoxic conditions, whereas those of pyruvate dehydrogenase subunits showed a 0.77-0.81-fold decrease. Protein levels of the fatty-acid synthesis enzymes, 3-ketoacyl-CoA thiolase isoforms (KAT1 and KAT2), 3-hydroxyacyl-CoA dehydrogenases, and acyl-CoA dehydrogenase were up-regulated by 1.20- to 1.42-fold in response to hypoxic treatment. Overall, our proteomic analysis revealed that wax ester synthesis-related enzymes are up-regulated at the protein level post-transcriptionally to promote wax ester production in E. gracilis under low-oxygen conditions.


gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission.
During sexual transmission of HIV in women, the first cells likely to be infected are submucosal CD4(+) T cells and dendritic cells of the lower genital tract. HIV is segregated from these target cells by an epithelial cell layer that can be bypassed even when healthy and intact. To understand how HIV penetrates this barrier, we identified a host protein, gp340, that is expressed on genital epithelium and binds the HIV envelope via a specific protein-protein interaction. This binding allows otherwise subinfectious amounts of HIV to efficiently infect target cells and allows this infection to occur over a longer period of time after binding. Our findings suggest a mechanism of viral entry during heterosexual transmission where HIV is bound to intact genital epithelia, which then promotes the initial events of infection. Understanding this step in the initiation of infection will allow for the development of tools and methods for blocking HIV transmission.


Temporal variation of planetary iron as a driver of evolution.
Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO2.


Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation.
The neural crest (NC) is a transient population of embryonic progenitors that are implicated in a diverse range of congenital birth defects and pediatric syndromes. The broad spectrum of NC-related disorders can be attributed to the wide variety of differentiated cell types arising from the NC. In vitro models of NC development provide a powerful platform for testing the relative contributions of intrinsic and extrinsic factors mediating NC differentiation under normal and pathogenic conditions. Although differentiation is a dynamic process that unfolds over time, currently, there is no well-defined chronology that characterizes the in vitro progression of NC differentiation towards specific cell fates. In this study, we have optimized culture conditions for expansion of primary murine NC cells that give rise to both ectodermal and mesoectodermal derivatives, even after multiple passages. Significantly, we have delineated highly reproducible timelines that include distinct intermediate stages for lineage-specific NC differentiation in vitro In addition, isolating both cranial and trunk NC cells from the same embryos enabled us to make direct comparisons between the two cell populations over the course of differentiation. Our results define characteristic changes in cell morphology and behavior that track the temporal progression of NC cells as they differentiate along the neuronal, glial and chondrogenic lineages in vitro These benchmarks constitute a chronological baseline for assessing how genetic or environmental disruptions may facilitate or impede NC differentiation. Introducing a temporal dimension substantially increases the power of this platform for screening drugs or chemicals for developmental toxicity or therapeutic potential. This article has an associated First Person interview with the first author of the paper.


Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?
Hepatitis B virus (HBV) polymerase is divided into terminal protein, spacer, reverse transcriptase, and RNase domains. Spacer has previously been considered dispensable, merely acting as a tether between other domains or providing plasticity to accommodate deletions and mutations. We explore evidence for the role of spacer sequence, structure, and function in HBV evolution and lineage, consider its associations with escape from drugs, vaccines, and immune responses, and review its potential impacts on disease outcomes.


On the Distribution of Tract Lengths During Adaptive Introgression.
Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.


Eu2+-Eu3+ valence transition in double, Eu-, and Na-doped PbSe from transport, magnetic, and electronic structure studies.
The Eu atoms in Pb1-xEuxSe have long been assumed to be divalent. We show that p-type doping of this magnetic semiconductor alloy with Na can modify the effective Eu valence: a mixed, Eu2+-Eu3+ state appears in Pb1-x-yEuxNaySe at particular values of y. Magnetization, carrier concentration, resistivity, and thermopower of Pb1-x-yEuxNaySe are reported for a number of samples with different x and y. A pronounced increase in thermopower at a given carrier concentration was identified and attributed to the presence of enhanced ionized impurity scattering. A strong decrease in the hole concentration is observed in Pb1-yNaySe when Eu is added to the system, which we attribute to a Eu2+-Eu3+ self-ionization process. This is evidenced by magnetization measurements, which reveal a significant reduction of the magnetic moment of Pb1-xEuxSe upon alloying with Na. Further, a deviation of magnetization from a purely paramagnetic state, described by a Brillouin function, identifies antiferromagnetic interactions between the nearest-neighbor Eu atoms: a value of Jex/kB = -0.35 K was found for the exchange coupling parameter. The conclusion of a Eu2+-Eu3+ self-ionization process being in effect is supported further by the electronic structure calculations, which show that an instability of the 4f7 configuration of the Eu2+ ion appears with Na doping. Schematically, it was found that the Eu 4f levels form states near enough to the Fermi energy that hole doping can lower the Fermi energy and trigger a reconfiguration of a 4f electronic shell.


Quantitative aspects of inhibition of virus replication by interferon in chick embryo cell cultures.
Hallum, J. V. (University of Pittsburgh, Pittsburgh, Pa.), and J. S. Youngner. Quantitative aspects of inhibition of virus replication by interferon in chick embryo cell cultures. J. Bacteriol. 92:1047-1050. 1966.-The effect of interferon on single cycles of replication of vesicular stomatitis virus and Mahoney poliovirus ribonucleic acid was studied in chick embryo cell cultures. The results showed that the titer of a given interferon preparation was independent of the input multiplicity of the challenge virus. In addition, the increase in virus yield with increasing virus challenge was a function of the number of infected cells, each of which yielded progeny at a level determined by the concentration of interferon to which the cells were exposed. These findings are not compatible with the concept that increases in the size of the virus challenge reverse or overcome protection of cells by interferon.


The rat SA gene shows genotype-dependent tissue-specific expression.
1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat. 2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes. 3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed. 4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus. 5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.


Identifying commercially relevant Echinacea species by AFLP molecular markers.
The rising interest in medicinal plants has brought several species of the genus Echinacea to the attention of many scientists. Echinacea angustifolia, E. pallida, and E. purpurea are the most important for their immunological properties, well known and widely used by the native Americans. The three species are easily distinguishable on the basis of their morphological characteristics, but it would be difficult, if not impossible, to distinguish them in commercial preparations of ground, dry plant parts of E. purpurea (the most valuable species for chemotherapeutic properties) mixed with the other two species. Species-specific molecular markers could be useful to address this issue. In the present work, using fresh material collected from cultivated Echinacea spp., AFLP analysis was used to discriminate the three species and to detect species-specific DNA fragments. By using 14 primer combinations it was possible to detect a total of 994 fragments, of which 565 were polymorphic. Overall, 89 fragments were unique to E. purpurea, 32 to E. angustifolia, and 26 to E. pallida. E+CAC/M+AAT or E+CAC/M+AGC alone provided 13, 9, and 4 or 7, 5, and 5 specific fragments for E. purpurea, E. angustifolia, and E. pallida, respectively. A validation trial to confirm the results was carried out on bulked samples of 23 accessions covering most of the genetic diversity of the three species. The results are discussed in terms of practical applications in the field of popular medicine, detecting frauds, and implications for the genus Echinacea.


Validation of a survey methodology for gastroesophageal reflux disease in China.
Gastroesophageal reflux disease (GERD) causes a wide range of clinical symptoms and potentially serious complications, but epidemiological data about GERD in China are limited. The aim of this pilot study was to develop and validate a methodology for the epidemiological study of GERD in China. Regionally stratified, randomized samples of Shanghai residents (n = 919) completed Mandarin translations of the Reflux Disease Questionnaire (RDQ), GERD Impact Scale, Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire and 36-item Short Form Health Survey (SF-36). Reliability and construct validity were tested by appropriate statistical analyses. The response rate was 86%. The test-retest reliability coefficients for the RDQ, GERD Impact Scale, QOLRAD and SF-36 were 0.80, 0.71, 0.93 and 0.96, respectively, and Cronbach's alpha coefficients were 0.86, 0.80, 0.98 and 0.90, respectively. Dimension scores were highly correlated with the total scores for the QOLRAD and SF-36, and factor analysis showed credible construct validity for the RDQ, GERD Impact Scale and SF-36. The RDQ GERD score was significantly negatively correlated with QOLRAD dimensions of food and drink problems and social functioning, and was significantly negatively correlated with all dimensions of the SF-36. All eight of the SF-36 dimensions were significantly correlated with the QOLRAD total score. This study developed and tested a successful survey methodology for the investigation of GERD in China. The questionnaires used demonstrated credible reliability and construct validity, supporting their use in larger epidemiological surveys of GERD in China.


The role of rain in dispersal of the primary inoculum of Plasmopara viticola.
Although primary infection of grapevines by Plasmopara viticola requires splash dispersal of inoculum from soil to leaves, little is known about the role of rain in primary inoculum dispersal. Distribution of rain splashes from soil to grapevine canopy was evaluated over 20 rain periods (0.2 to 64.2 mm of rain) with splash samplers placed within the canopy. Samplers at 40, 80, and 140 cm above the soil caught 4.4, 0.03, and 0.003 drops/cm(2) of sampler area, respectively. Drops caught at 40 and 80 cm (1.5 cm in diameter) were larger than drops at 140 cm (1.3 cm). Leaf coverage by splashed drops, total drop number, and drop size increased with an increase in the maximum intensity of rain (mm/h) during any rain period. Any rainfall led to infection in potted grapevines placed outside on leaf litter containing oospores, if the litter contained germinated oospores at the time of rain; infection severity was unrelated to rain amount or intensity. Results from vineyards also indicate that any rain can carry P. viticola inoculum from soil to leaves and should be considered a splash event in disease prediction systems. Sampling for early disease detection should focus on the lower canopy, where the probability of splash impact is greatest.


First Report of Fusarium Stem and Crown Rot of Fennel in Arizona Caused by Fusarium avenaceum.
In 2010 in Yuma, AZ, field-grown fennel (Foeniculum vulgare, Apiaceae) exhibited previously undescribed disease symptoms. The lower stems in contact with soil developed a brown decay and leaves on these stems became chlorotic. White mycelium and orange sporodochia were observed on affected tissues near the soil line. Diseased stems later wilted, died, and resulted in reduced quality of the fennel; these plants were not harvested. Disease distribution was patchy and prevalence was approximately 5%. Symptomatic tissues were surface sterilized in a dilute (1%) bleach solution for 3 min and tissues from the margins of the decay were placed into petri plates containing acidified corn meal agar (2 ml of 25% lactic acid/liter). Isolations consistently resulted in the recovery of a presumptive Fusarium species. Isolates were transferred to carnation leaf agar and incubated at 22°C under fluorescent lights for 10 days. Morphologies of all isolates were identical, with macroconidia being long and slender, slightly curved, with elongated, bent apical cells and notched basal cells. Conidia were borne on monophialides. Microconidia were sparse and chlamydospores were not observed. For two isolates, a portion of the translation elongation factor 1-alpha gene (TEF) was amplified with primers ef1 and ef2 (3). Based on a comparison of 668 base pairs, both isolates had the same sequence, which differed by one base pair from an accession (GQ915502.1) of Fusarium avenaceum in GenBank. The same single base pair also separated the two fennel isolates from an isolate of F. avenaceum (GL 13) previously recovered from Eustoma grandiflorum (=Lisianthus russellianus) (2). Thus, both morphological and molecular criteria support identification of the recovered fungus as F. avenaceum (Fries) Saccardo. Partial TEF sequences were deposited in GenBank (Accession Nos. JN254784, JN254785, and JN254786 for the two fennel isolates and GL 13, respectively). All isolates are archived in the Department of Plant Pathology at University of California, Davis. Pathogenicity was tested by cutting shallow slits into fennel stems, inserting one colonized agar plug into each cut, and wrapping the stems with Parafilm. Five isolates from fennel were tested on 10 stems each. Control plants were inoculated with uncolonized agar plugs. Plants were maintained at 24 to 26°C in a greenhouse. After 6 to 8 days, a brown decay developed on 70 to 90% of Fusarium-inoculated stems at the points of inoculation. Foliage later became chlorotic and F. avenaceum was recovered from all symptomatic stems. Control plants were symptomless. The experiment was completed two times and results were the same. In addition, F. avenaceum isolate GL13 from E. grandiflorum (2) was inoculated onto fennel plants with the same method. However, these inoculated plants remained symptomless. To our knowledge, this is the first report of a stem and crown rot disease of fennel caused by F. avenaceum. Apparently, the only other published account of a Fusarium disease of fennel is root rot caused by F. solani (1). The inability of the Eustoma isolate of F. avenaceum to cause disease in fennel suggests that these two crown rot pathogens may have restricted host ranges. References: (1) J. H. Gupta and V. P. Srivastava. Indian J. Mycol. Plant Pathol. 8:206, 1979. (2) S. T. Koike et al. Plant Dis. 80:1429, 1996. (3) K. O'Donnell et al. Proc. Nat. Acad. Sci. U.S.A. 95:2044, 1998.


Analysis of the brain mural cell transcriptome.
Pericytes, the mural cells of blood microvessels, regulate microvascular development and function and have been implicated in many brain diseases. However, due to a paucity of defining markers, pericyte identification and functional characterization remain ambiguous and data interpretation problematic. In mice carrying two transgenic reporters, Pdgfrb-eGFP and NG2-DsRed, we found that double-positive cells were vascular mural cells, while the single reporters marked additional, but non-overlapping, neuroglial cells. Double-positive cells were isolated by fluorescence-activated cell sorting (FACS) and analyzed by RNA sequencing. To reveal defining patterns of mural cell transcripts, we compared the RNA sequencing data with data from four previously published studies. The meta-analysis provided a conservative catalogue of 260 brain mural cell-enriched gene transcripts. We validated pericyte-specific expression of two novel markers, vitronectin (Vtn) and interferon-induced transmembrane protein 1 (Ifitm1), using fluorescent in situ hybridization and immunohistochemistry. We further analyzed signaling pathways and interaction networks of the pericyte-enriched genes in silico. This work provides novel insight into the molecular composition of brain mural cells. The reported gene catalogue facilitates identification of brain pericytes by providing numerous new candidate marker genes and is a rich source for new hypotheses for future studies of brain mural cell physiology and pathophysiology.


"Not Only Adults Can Make Good Decisions, We as Children Can Do That as Well" Evaluating the Process of the Youth-Led Participatory Action Research 'Kids in Action'.
In Youth-led Participatory Action Research (YPAR), youth collaborate with academic researchers to study a problem, develop actions that align with their needs and interests, and become empowered. 'Kids in Action' aimed to develop actions targeting healthy physical activity and dietary behavior among, and together with, 9-12-year-old children as co-researchers. This paper presents the process evaluation of 'Kids in Action' based on eight focus groups with children (N = 40) and eight interviews with community partners (N = 11). Interview guides were based on empowerment theory and the RE-AIM framework, in order to evaluate the study on: empowerment, collaborations, reach, effectiveness, adoption, implementation, and maintenance. Transcripts were analyzed using evaluation and provisional coding. Both children and community partners perceived an increased awareness of healthy behaviors and an improvement in confidence, critical awareness, leadership and collaboration skills, which contributed to increased feelings of empowerment. Community partners valued child participation and the co-created actions. Actions were also well-perceived by children and they liked being involved in action development. The strong relationship of researchers with both children and relevant community partners proved an important facilitator of co-creation. Future studies are recommended to attempt closer collaboration with schools and parents to gain even more support for co-created actions and increase their effectiveness.


Interaction of dietary fat and route of carcinogen administration on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats.
Since the results of an earlier study indicating no effect of dietary fat on dimethylhydrazine (DMH)-induced colon cancer in rats differed from those of other investigators, the present study was initiated to determine if the modulating effect of fat intake on colon tumorigenesis was dependent on the route of DMH administration. Male weanling Sprague-Dawley rats (160) were fed one of two nutritionally balanced diets containing 5% or 24% corn oil (CO). Following 3 weeks adaptation to their respective diets, 40 rats from each diet group were treated with five doses of DMH (30 mg/kg) by intragastric (i.g.) gavage or subcutaneous (s.c.) injection, over a 3 week period. Rats were sacrificed when they showed clinical signs of colon tumor and surviving animals were killed 51 weeks after the initial DMH treatment. The cumulative probability of death with colon carcinoma did not differ between the dietary or treatment groups. There was no effect of route of administration or dietary fat on total intestinal tumor incidence. The number of rats with colon carcinoma was: 5% CO.IG = 25; 24% CO.IG = 27; 5% CO.SC = 23; 24% CO.SC = 19. Polypoid tumor incidence was significantly higher in the 24% CO.SC group (12/40) compared to the 5% CO.SC group (3/40) (Chi-squared = 5.25; p less than 0.03) while sessile tumor incidence was the inverse. Marginally significant differences in tumor morphology were noted between the IG groups.


Opportunities for High-plex Spatial Transcriptomics in Solid Organ Transplantation.
The last 5 y have seen the development and widespread adoption of high-plex spatial transcriptomic technology. This technique detects and quantifies mRNA transcripts in situ, meaning that transcriptomic signatures can be sampled from specific cells, structures, lesions, or anatomical regions while conserving the physical relationships that exist within complex tissues. These methods now frequently implement next-generation sequencing, enabling the simultaneous measurement of many targets, up to and including the whole mRNA transcriptome. To date, spatial transcriptomics has been foremost used in the fields of neuroscience and oncology, but there is potential for its use in transplantation sciences. Transplantation has a clear dependence on biopsies for diagnosis, monitoring, and research. Transplant patients represent a unique cohort with multiple organs of interest, clinical courses, demographics, and immunosuppressive regimens. Obtaining high complexity data on the disease processes underlying rejection, tolerance, infection, malignancy, and injury could identify new opportunities for therapeutic intervention and biomarker identification. In this review, we discuss currently available spatial transcriptomic technologies and how they can be applied to transplantation.


Comparison between survey radiography, B-mode ultrasonography, contrast-enhanced ultrasonography and contrast-enhanced multi-detector computed tomography findings in dogs with acute abdominal signs.
Contrast-enhanced multi-detector computed tomography (CE-MDCT) is used routinely in evaluating human patients with acute abdominal symptoms. Contrast-enhanced ultrasound (CEUS) continues to be in its infancy as it relates to evaluation of the acute abdomen. The purpose of this study was to compare survey radiography, B-mode ultrasound, CEUS, and CE-MDCT findings in canine patients presenting with acute abdominal signs; with a focus on the ability to differentiate surgical from non-surgical conditions. Nineteen dogs were prospectively enrolled. Inclusion required a clinical diagnosis of acute abdominal signs and confirmed surgical or non-surgical causes for the clinical signs. Agreement for the majority of recorded imaging features was at least moderate. There was poor agreement in the identification of pneumoperitoneum and in the comparison of pancreatic lesion dimensions for B-mode vs. CEUS. The CT feature of fat stranding was detected in cases including, but not limited to, gastric neoplasia with perforation, pancreatitis, and small intestinal foreign body. Ultrasound underestimated the size and number of specific lesions when compared with CE-MDCT. Contrast-enhanced ultrasound was successful in detecting bowel and pancreatic perfusion deficits that CE-MDCT failed to identify. Accuracy for differentiation of surgical vs. non-surgical conditions was high for all modalities; 100%, 94%, and 94% for CE-MDCT, ultrasonography and survey radiography respectively. Findings indicated that CE-MDCT is an accurate screening test for differentiating surgical from non-surgical acute abdominal conditions in dogs. Focused CEUS following CE-MDCT or B-mode ultrasonography may be beneficial for identifying potentially significant hypoperfused lesions.


Antidepressant Medication Use Among Patients with Depression: Comparison between Usual Care and Collaborative Care Using Care Managers.
Depression poses a significant economic and health burden, yet it remains underdiagnosed and inadequately treated. The STAR*D trial funded by the National Institute of Mental Health showed that more than one antidepressant medication is often necessary to achieve disease remission among patients seen in both psychiatric and primary care settings. The collaborative care model (CCM), using care managers, has been shown to be effective in numerous studies in achieving sustained outcomes in depression management compared to usual care. This model was adopted in a statewide depression treatment improvement initiative among primary care clinics in Minnesota, which was launched in March 2008. In this study, records of patients who were enrolled in CCM from March 2008 until March 2009 were reviewed and compared to those under usual care. Patients who were followed under the CCM had a significantly greater number of antidepressant medication utilizations when compared to those under usual care. After 6 months, mean PHQ-9 score of patients under CCM was statistically lower than those in usual care. There was no significant difference in both mean PHQ-9 scores at 6 months and antidepressant utilization between the 2 groups among patients aged 65 years and older.


Mapping of avirulence genes in the rice blast fungus, Magnaporthe grisea, with RFLP and RAPD markers.
Three genetically independent avirulence genes, AVR1-Irat7, AVRI-MedNoi; and AVR1-Ku86, were identified in a cross involving isolates Guy11 and 2/0/3 of the rice blast fungus, Magnaporthe grisea. Using 76 random progeny, we constructed a partial genetic map with restriction fragment length polymorphism (RFLP) markers revealed by probes such as the repeated sequences MGL/MGR583 and Pot3/MGR586, cosmids from the M. grisea genetic map, and a telomere sequence oligonucleotide. Avirulence genes AVR1-MedNoi and AVR1-Ku86 were closely linked to telomere RFLPs such as marker TelG (6 cM from AVR1-MedNoi) and TelF (4.5 cM from AVR1-Ku86). Avirulence gene AVR1-Irat7 was linked to a cosmid RFLP located on chromosome 1 and mapped at 20 cM from the avirulence gene AVR1-CO39. Using bulked segregant analysis, we identified 11 random amplified polymorphic DNA (RAPD) markers closely linked (0 to 10 cM) to the avirulence genes segregating in this cross. Most of these RAPD markers corresponded to junction fragments between known or new transposons and a single-copy sequence. Such junctions or the whole sequences of single-copy RAPD markers were frequently absent in one parental isolate. Single-copy sequences from RAPD markers tightly linked to avirulence genes will be used for positional cloning.


Abciximab in the treatment of acute myocardial infarction eligible for primary percutaneous transluminal coronary angioplasty. Results of the Glycoprotein Receptor Antagonist Patency Evaluation (GRAPE) pilot study.
We sought to study the effect of early infusion of abciximab on coronary patency before primary angioplasty in patients with acute myocardial infarction. Glycoprotein IIb/IIIa antagonists have proved to be effective in reducing ischemic events associated with coronary angioplasty. The present study explores whether abciximab alone, without administration of thrombolytic therapy, may induce reperfusion in patients with acute myocardial infarction. In the Glycoprotein Receptor Antagonist Patency Evaluation pilot study 60 patients with less than 6 h signs and symptoms of acute myocardial infarction eligible for primary angioplasty received in the emergency room a bolus of abciximab 250 microg/kg followed by a 12-h infusion of 10 microg/min. All patients were also treated with an oral dose of 160 mg aspirin and 5,000 IU of heparin intravenously. As soon as possible a diagnostic angiography was performed to evaluate the patency of the infarct-related artery. The median time between onset of symptoms and the administration of the abciximab bolus was 150 min (range 45 to 345), and the median time between abciximab bolus and first contrast injection in the infarct-related artery was 45 min (range 10 to 150). In 24 patients (40%, 95% confidence interval 28% to 52%) Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at a median time of 45 min (range 10 to 150) after abciximab bolus; TIMI flow grade 3 was observed in 11 patients (18%, 95% confidence interval 9% to 28%). There was no difference in percentage of TIMI flow grade 2 or 3 between patients who received abciximab within 2.5 h after onset of symptoms or thereafter. Abciximab therapy given in the emergency room in patients awaiting primary angioplasty is associated with full reperfusion (TIMI flow grade 3) in about 20% and with TIMI flow grade 2 or 3 in about 40% of the patients at a median time of 45 min. These figures are higher than those in primary angioplasty trials without such pretreatment. Randomized controlled trials of very early infusion of abciximab, either prehospital or in-hospital, in patients eligible for angioplasty are warranted.


Copper radical oxidases: galactose oxidase, glyoxal oxidase, and beyond!
The copper radical oxidases (CROs) are an evolutionary and functionally diverse group of enzymes established by the historically significant galactose 6-oxidase and glyoxal oxidase from fungi. Inducted in 2013, CROs now constitute Auxiliary Activity Family 5 (AA5) in the Carbohydrate-Active Enzymes (CAZy) classification. CROs catalyse the two-electron oxidation of their substrates using oxygen as the final electron acceptor and are particularly distinguished by a cross-linked tyrosine-cysteine co-factor that is integral to radical stabilization. Recently, there has been a significant increase in the biochemically and structurally characterized CROs, which has revealed an expanded natural diversity of catalytic activities in the family. This review provides a brief historical introduction to CRO biochemistry and structural biology as a foundation for an update on current advances in CRO enzymology, biotechnology, and biology across kingdoms of life.


RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein.
RASSF1A is a tumor suppressor gene that is epigenetically silenced in a wide variety of sporadic human malignancies. Expression of alternative RASSF1 isoforms cannot substitute for RASSF1A-promoted cell-cycle arrest and apoptosis. Apoptosis can be driven by either activating Bax or by activation of MST kinases. The Raf1 proto-oncogene binds to MST2, preventing its activation and proapoptotic signaling. Here we show that key steps in RASSF1A-induced apoptosis are the disruption of the inhibitory Raf1-MST2 complex by RASSF1A and the concomitant enhancement of MST2 interaction with its substrate, LATS1. Subsequently, RASSF1A-activated LATS1 phosphorylates and releases the transcriptional regulator YAP1, allowing YAP1 to translocate to the nucleus and associate with p73, resulting in transcription of the proapoptotic target gene puma. Our results describe an MST2-dependent effector pathway for RASSF1A proapoptotic signaling and indicate that silencing of RASSF1A in tumors removes a proapoptotic signal emanating from p73.


Costs and benefits of implementing an Environmental Speed Limit in a Nordic city.
We present a comprehensive study on the impacts and associated changes in costs resulting from the implementation of Environmental Speed Limits (ESLs), as a measure to reduce PM10 and associated health effects. We present detailed modelled emissions (i.e., CO2, NOx, PM2.5 and PM10), concentration levels (i.e., PM2.5 and PM10) and population exposure to PM2.5 and PM10 under three scenarios of ESL implementation for the Metropolitan Area of Oslo. We find that whilst emissions of NOx and CO2 do not seem to show significant changes with ESL implementation, PM10 emissions are reduced by 6-12% and annual concentration levels are reduced up to 8%, with a subsequent reduction in population exposure. The modelled data is used to carry out a detailed analysis to quantify the changes in private and social costs for the roads in Oslo where ESL are implemented today. This involves assessments related to human health, climate, fuel consumption, time losses and the incidence of traffic accidents. For a scenario using actual speed data from ESL implementation, our study shows a net benefit associated with the implementation of ESLs, whilst for a theoretical scenario with strict speed limit compliance we find a net increase in costs. This is largely due to variation in costs due to time losses between the scenarios, although uncertainties are high.


Systemic lupus erythematosus flare up as acute spinal subarachnoid hemorrhage with bilateral lower limb paralysis.
Subarachnoid hemorrhage (SAH) is an uncommon complication of systemic lupus erythematosus (SLE). Solitary association of fatal spinal SAH as a complication of SLE, has not been encountered much in literature although coexisting acute cerebral and spinal SAH have been associated with SLE. We present a 39-year old female with initial diagnosis of SLE eight years ago who suddenly developed a productive cough, acute abdomen and paralysis of the lower limbs. Magnetic resonance imaging of the spine revealed thoracic spinal SAH with varying degrees of thoracic spinal cord compression. The hemorrhage was total evacuated via surgery. She regained normal function of her lower limbers after the operation with no further neurological complications. One of the rare but fatal complications of SLE is solitary spinal SAH without cranial involvement. The best and most appropriate management of this kind of presentation is surgical decompression of the hematoma with total hemostasis. The cause of hemorrhage should be identified intra-operatively and treated appropriately.


Insights into the quaternary association of proteins through structure graphs: a case study of lectins.
The unique three-dimensional structure of both monomeric and oligomeric proteins is encoded in their sequence. The biological functions of proteins are dependent on their tertiary and quaternary structures, and hence it is important to understand the determinants of quaternary association in proteins. Although a large number of investigations have been carried out in this direction, the underlying principles of protein oligomerization are yet to be completely understood. Recently, new insights into this problem have been gained from the analysis of structure graphs of proteins belonging to the legume lectin family. The legume lectins are an interesting family of proteins with very similar tertiary structures but varied quaternary structures. Hence they have become a very good model with which to analyse the role of primary structures in determining the modes of quaternary association. The present review summarizes the results of a legume lectin study as well as those obtained from a similar analysis carried out here on the animal lectins, namely galectins, pentraxins, calnexin, calreticulin and rhesus rotavirus Vp4 sialic-acid-binding domain. The lectin structure graphs have been used to obtain clusters of non-covalently interacting amino acid residues at the intersubunit interfaces. The present study, performed along with traditional sequence alignment methods, has provided the signature sequence motifs for different kinds of quaternary association seen in lectins. Furthermore, the network representation of the lectin oligomers has enabled us to detect the residues which make extensive interactions ('hubs') across the oligomeric interfaces that can be targetted for interface-destabilizing mutations. The present review also provides an overview of the methodology involved in representing oligomeric protein structures as connected networks of amino acid residues. Further, it illustrates the potential of such a representation in elucidating the structural determinants of protein-protein association in general and will be of significance to protein chemists and structural biologists.


Induction of angiogenesis and neovascularization in adjacent tissue of plasma-collagen-coated silicone implants.
Formation of encapsulating, avascular fibrous tissue is deemed to decrease implant's biocompatibility and versatility. We investigated whether plasma-mediated collagen coating possesses the ability to enhance neovascularization in the vicinity of silicone implants. Plasma-treated collagen-I-coated silicone samples were placed into the dorsal skinfold chambers of female balb/c mice (n = 10). Conventional silicone served as control (n = 10). Intravital microscopy was performed within implant's surrounding tissue on days 1, 5, and 10. Functional vessel density, intervascular distance, vessel diameter, microvascular permeability, red blood cell velocity, and leukocyte-endothelium interaction were determined. Enhanced angiogenesis in the tissue surrounding plasma-pretreated collagen-coated implants was noted. Significant increase of functional vessel density due to vascular new development was observed (t test, P < .05). Analyses of microvascular permeability and red blood cell velocity displayed stable perfusion of the vascular network neighboring the surface-modified implants. Intensified vascularity due to induced angiogenesis and neovascularization in the tissue surrounding plasma-collagen-coated samples were observed. These results indicate that plasma-mediated collagen coating might be a promising technology in order to improve the biocompatibility and versatility of silicone implants.


Copy Number Heterogeneity of JC Virus Standards.
Quantitative PCR is a diagnostic mainstay of clinical virology, and accurate quantitation of viral load among labs requires the use of international standards. However, the use of multiple passages of viral isolates to obtain sufficient material for international standards may result in genomic changes that complicate their use as quantitative standards. We performed next-generation sequencing to obtain single-nucleotide resolution and relative copy number of JC virus (JCV) clinical standards. Strikingly, the WHO international standard and the Exact v1/v2 prototype standards for JCV showed 8-fold and 4-fold variation in genomic coverage between different loci in the viral genome, respectively, due to large deletions in the large T antigen region. Intriguingly, several of the JCV standards sequenced in this study with large T antigen deletions were cultured in cell lines immortalized using simian virus 40 (SV40) T antigen, suggesting the possibility of transcomplementation in cell culture. Using a cutoff 5% allele fraction for junctional reads, 7 different rearrangements were present in the JC virus sequences present in the WHO standard across multiple library preparations and sequencing runs. Neither the copy number differences nor the rearrangements were observed in a clinical sample with a high copy number of JCV or a plasmid control. These results were also confirmed by the quantitative real-time PCR (qPCR), droplet digital PCR (ddPCR), and Sanger sequencing of multiple rearrangements. In summary, targeting different regions of the same international standard can result in up to an 8-fold difference in quantitation. We recommend the use of next-generation sequencing to validate standards in clinical virology.


Inexpensive method for producing macroporous silicon particulates (MPSPs) with pyrolyzed polyacrylonitrile for lithium ion batteries.
One of the most exciting areas in lithium ion batteries is engineering structured silicon anodes. These new materials promise to lead the next generation of batteries with significantly higher reversible charge capacity than current technologies. One drawback of these materials is that their production involves costly processing steps, limiting their application in commercial lithium ion batteries. In this report we present an inexpensive method for synthesizing macroporous silicon particulates (MPSPs). After being mixed with polyacrylonitrile (PAN) and pyrolyzed, MPSPs can alloy with lithium, resulting in capacities of 1000 mAhg(-1) for over 600+ cycles. These sponge-like MPSPs with pyrolyzed PAN (PPAN) can accommodate the large volume expansion associated with silicon lithiation. This performance combined with low cost processing yields a competitive anode material that will have an immediate and direct application in lithium ion batteries.


Thioesterase domains of fungal nonreducing polyketide synthases act as decision gates during combinatorial biosynthesis.
A crucial step during the programmed biosynthesis of fungal polyketide natural products is the release of the final polyketide intermediate from the iterative polyketide synthases (iPKSs), most frequently by a thioesterase (TE) domain. Realization of combinatorial biosynthesis with iPKSs requires TE domains that can accept altered polyketide intermediates generated by hybrid synthase enzymes and successfully release "unnatural products" with the desired structure. Achieving precise control over product release is of paramount importance with O-C bond-forming TE domains capable of macrocyclization, hydrolysis, transesterification, and pyrone formation that channel reactive, pluripotent polyketide intermediates to defined structural classes of bioactive secondary metabolites. By exploiting chimeric iPKS enzymes to offer substrates with controlled structural variety to two orthologous O-C bond-forming TE domains in situ, we show that these enzymes act as nonequivalent decision gates, determining context-dependent release mechanisms and overall product flux. Inappropriate choice of a TE could eradicate product formation in an otherwise highly productive chassis. Conversely, a judicious choice of a TE may allow the production of a desired hybrid metabolite. Finally, a serendipitous choice of a TE may reveal the unexpected productivity of some chassis. The ultimate decision gating role of TE domains influences the observable outcome of combinatorial domain swaps, emphasizing that the deduced programming rules are context dependent. These factors may complicate engineering the biosynthesis of a desired "unnatural product" but may also open additional avenues to create biosynthetic novelty based on fungal nonreduced polyketides.


Effect of brewery wastewater obtained from different phases of treatment plant on seed germination of chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea (Cajanus cajan).
Brewing industry releases large quantities of wastewater after product generation. Brewery wastewater contains organic compounds which are biodegradable in nature. These biodegradable wastes can be recycled and reused and hence considered as suitable products for agriculture. But before using wastewater for agriculture, it is better to evaluate the phytotoxic effects of wastewater on crops. Hence, the main objective of this study is to evaluate the effects of brewery effluent on seed germination and growth parameters of selected crop species like chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea (Cajanus cajan). Study comprised seven types of water treatments-tap water as control, diluted UASBR effluent (50% effluent + 50% distilled water): UASBR50, undiluted UASBR effluent: UASBR100, diluted TC effluent (50% effluent + 50% distilled water): ETP50,TC effluent without dilution: ETP100, 10% diluted reverse osmosis (RO10) reject (10% RO reject + 90% distilled water), and 25% diluted reverse osmosis(RO25) reject (25% RO reject + 75% distilled water) with three replications in completely randomized design. Germination test was performed in petri plates for 5 days. Parameters like germination percentage, germination rate index, seedling length, phytotoxicity index, seed vigor index, and biomass were calculated. All parameters decreased with increase in respective effluent concentration. Among all treatments, RO25 showed highest inhibitory effect on all three crops. Even though undiluted effluent of UASBR and ETP effluent showed positive effect on germination, seedling growth of three crops was promoted to the maximum by UASBR50 and ETP50. Hence, from the study, it was concluded that dilution of brewery effluent can be recommended before using it for irrigational purpose.


Effect of Lung Surfactant Protein SP-C and SP-C-Promoted Membrane Fragmentation on Cholesterol Dynamics.
To allow breathing and prevent alveolar collapse, lung surfactant (LS) develops a complex membranous system at the respiratory surface. LS is defined by a specific protein and lipid composition, including saturated and unsaturated phospholipid species and cholesterol. Surfactant protein C (SP-C) has been suggested to be an essential element for sustaining the presence of cholesterol in surfactant without functional impairment. In this work, we used a fluorescent sterol-partitioning assay to assess the effect of the surfactant proteins SP-B and SP-C on cholesterol distribution in membranes. Our results suggest that in the LS context, the combined action of SP-B and SP-C appears to facilitate cholesterol dynamics, whereas SP-C does not seem to establish a direct interaction with cholesterol that could increase the partition of free cholesterol into membranes. Interestingly, SP-C exhibits a membrane-fragmentation behavior, leading to the conversion of large unilamellar vesicles into highly curved vesicles ∼25 nm in diameter. Sterol partition was observed to be sensitive to the bending of bilayers, indicating that the effect of SP-C to mobilize cholesterol could be indirectly associated with SP-C-mediated membrane remodeling. Our results suggest a potential role for SP-C in generating small surfactant structures that may participate in cholesterol mobilization and pulmonary surfactant homeostasis at the alveolar interfaces.


The function of the alula in avian flight.
The alula is a small structure located at the joint between the hand-wing and arm-wing of birds and is known to be used in slow flight with high angles of attack such as landing. It is assumed to function similarly to a leading-edge slat that increases lift and delays stall. However, in spite of its universal presence in flying birds and the wide acceptance of stall delay as its main function, how the alula delays the stall and aids the flight of birds remains unclear. Here, we investigated the function of alula on the aerodynamic performance of avian wings based on data from flight tasks and wind-tunnel experiments. With the alula, the birds performed steeper descending flights with greater changes in body orientation. Force measurements revealed that the alula increases the lift and often delays the stall. Digital particle image velocimetry showed that these effects are caused by the streamwise vortex, formed at the tip of the alula, that induces strong downwash and suppresses the flow separation over the wing surface. This is the first experimental evidence that the alula functions as a vortex generator that increases the lift force and enhances manoeuvrability in flights at high angles of attack.


WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys.
The compound WR 238605 is a primaquine analog being developed by the U.S. Army as an antimalarial drug. Currently, there is no established treatment for Plasmodium vivax parasitemias that are not cured by chloroquine. This study tested WR 238605, chloroquine, and their combinations against a chloroquine-resistant strain of P. vivax (AMRU 1) in Aotus monkeys. A total dose of 3 mg/kg of WR 238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites in all eight monkeys but recrudescence of parasitemia occurred 15-25 days after initiation of treatment. A total dose of 9 mg/kg of WR 238605 over a three-day period cured all three monkeys of their infections. A total dose of 30 mg/kg of chloroquine did not clear patent infections in three monkeys, whereas a total dose of 60 mg/kg generally (two of three) cleared patent parasitemia but did not cure. Whereas total doses of 30 mg/kg of chloroquine or 3 mg/kg of WR 238605 given alone failed to cure, both drugs given in combination at these dosages cured two of three infections. These results indicate that WR 238605 may be an alternative treatment for chloroquine-resistant vivax malaria.


Kaposi's sarcoma and non-Hodgkin's lymphomas in children and adolescents with AIDS.
To assess the proportion of, and the characteristics associated with, Kaposi's sarcoma (KS) and non-Hodgkin's lymphomas (NHL) in children (0-12 years) and adolescents (13-19 years) at AIDS diagnosis, in Europe and in the United States (US). Comparison of the proportions of KS and NHL at AIDS diagnosis, according to various characteristics, by means of the European Non-Aggregate AIDS Data Set (4400 children and 764 adolescents) and the US AIDS Public Information Data Set (4710 children and 1064 adolescents) updated to June 1993. Comparison of data was made using odds ratios (OR) and corresponding 95% confidence intervals. Between 0 and 19 years, the proportion of KS at AIDS diagnosis (0.5% in Europe and 0.9% in the US) increased with age, particularly in Europe, and was higher in males than in females. It decreased with time in the US but not in Europe. In the US, black children showed a nearly threefold excess of KS as compared with white children. Adolescents who reported homosexual intercourse with other males had significantly elevated risks of KS, both in Europe (OR, 6.3) and in the US (OR, 21.1). NHL was diagnosed in 0.9% of children in Europe and in 1.5% in the US. The proportion of NHL significantly increased with age (3.1% among adolescents in Europe and 3.0% in the US), and was higher in males than in females. In the US, NHL tended to decline in proportion with all AIDS cases over time and showed a nearly twofold higher frequency in white children. No association emerged between NHL and HIV transmission category. In agreement with incidence rates in the general paediatric population, but at variance with AIDS in adults, NHL turned out to be more common than KS in children and adolescents with AIDS. A strong excess of KS was already present in adolescents who reported homosexual intercourse.


Reporting of Resistance Training Dose, Adherence, and Tolerance in Exercise Oncology.
While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise science, there is inadequate detail facilitating the standardized reporting of resistance training adherence in the oncology setting. The purpose of this study was to apply a novel method to report resistance training dose, adherence, and tolerance in patients with cancer. A total of 47 prostate cancer patients (70.1 ± 8.9 yr, body mass index, 28.6 ± 4.0) with bone metastatic disease completed an exercise program for 12 wk. We assessed traditional metrics of adherence (attendance and loss to follow-up), in addition to novel proposed metrics (exercise-relative dose intensity, dose modification, and exercise interruption). Total training volume in kilograms (repetitions × sets × training load (weight)) was calculated for each patient. Attendance assessed from traditional metrics was 79.5% ± 17.0% and four patients (9%) were lost to follow-up. The prescribed and actual cumulative total dose of resistance training was 139,886 ± 69,150 kg and 112,835 ± 83,499 kg, respectively, with a mean exercise-relative dose intensity of 77.4% ± 16.6% (range: 19.4% -99.4%). Resistance training was missed (1-2 consecutive sessions) or interrupted (missed ≥3 consecutive sessions) in 41 (87%) and 24 (51%) participants, respectively. Training dose was modified (reduction in sets, repetitions, or weight) in 40 (85%) of patients. Importantly, using attendance as a traditional metric of adherence, these sessions would have all counted as adherence to the protocol. Traditional reporting metrics of resistance training in exercise oncology may overestimate exercise adherence. Our proposed metrics to capture resistance training dose, adherence, and tolerance may have important applications for future studies and clinical practice.


Molecular therapy targeting Sonic hedgehog and hepatocyte growth factor signaling in a mouse model of medulloblastoma.
The use of genetically engineered mice has provided insights into the molecular pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar neural progenitor cells induces medulloblastomas in mice, and coexpression of hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine whether Shh + HGF-driven medulloblastomas were responsive to Shh signaling blockade and whether treatment response could be enhanced by combination therapy targeting both HGF and Shh signaling pathways, we carried out a survival study in mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and HGF, after which we treated the mice systemically with (a) HGF-neutralizing monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh-neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1. We report that monotherapy targeting either HGF signaling or Shh signaling prolonged survival and that anti-HGF therapy had a more durable response than Shh-targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative survival was equivalent to that of L2G7 monotherapy and that of L2G7 + cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF-targeted therapies inhibited tumor growth was a potent apoptotic death response in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF-induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active.


Kinetic analysis of 3'-deoxy-3'-fluorothymidine PET studies: validation studies in patients with lung cancer.
Assessing cellular proliferation provides a direct method to measure the in vivo growth of cancer. We evaluated the application of a model of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) kinetics described in a companion report to the analysis of FLT PET image data in lung cancer patients. Compartmental model analysis was performed to estimate the overall flux constants (K(FLT)) for FLT phosphorylation in tumor, bone marrow, and muscle. Estimates of flux were compared with an in vitro assay of proliferation (Ki-67) applied to tissue derived from surgical resection. Compartmental modeling results were compared with simple model-independent methods of estimating FLT uptake. Seventeen patients with 18 tumor sites underwent up to 2 h of dynamic PET with blood sampling. Metabolite analysis of plasma samples corrected the total blood activity for labeled metabolites and provided the FLT model input function. A 2-compartment, 4-parameter model (4P) was tested and compared with a 2-compartment, 3-parameter (3P) model for estimating K(FLT). Bone marrow, a proliferative normal tissue, had the highest values of K(FLT), whereas muscle, a nonproliferating tissue, showed the lowest values. The K(FLT) for tumors estimated by compartmental analysis had a fair correlation with estimates by modified graphical analysis (r = 0.86) and a poorer correlation with the average standardized uptake value (r = 0.62) in tumor. Estimates of K(FLT) derived from 60 min of dynamic PET data using the 3P model underestimated K(FLT) compared with 90 or 120 min of dynamic data analyzed using the 4P model. Comparison of flux estimates with an independent measure of cellular proliferation showed that K(FLT) was highly correlated with Ki-67 (Spearman rho = 0.92, P < 0.001). Ignoring the metabolites of FLT in blood underestimated K(FLT) by as much as 47%. Compartmental analysis of FLT PET image data yielded robust estimates of K(FLT) that correlated with in vitro measures of tumor proliferation. This method can be applied generally to other imaging studies of different cancers after validation of parameter error. Tumor loss of phosphorylated FLT nucleotides (k(4)) is notable and leads to errors when FLT uptake is evaluated using model-independent approaches that ignore k(4), such as graphical analysis or the SUV.


Programming social, cognitive, and neuroendocrine development by early exposure to novelty.
Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (i) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (ii) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.


Diet quality of Australian breast cancer survivors: a cross-sectional analysis from the Australian Longitudinal Study on Women's Health.
Evidence supports strong associations between healthful eating patterns and maintaining a healthy weight with favourable health outcomes for breast cancer survivors (BCS). The present study aimed to evaluate the diet quality of Australian BCS and to determine whether diet quality differed between BCS and age-matched healthy controls (HC) or by geographical location. This cross-sectional study included 281 BCS and 4069 HC from the Australian Longitudinal Study on Women's Health mid-aged cohort completing Survey 3 in 2001. Data from the Dietary Questionnaire for Epidemiological Studies food frequency questionnaire were used to calculate the Australian Recommended Food Score (ARFS), a validated summary estimate of diet quality based on adherence to the Australian dietary guidelines. The mean (SD) ARFS of the BCS group was 33.2 (9.4) out of a maximum of 74. Mean (SD) total ARFS and component scores of BCS did not differ from the HC group [32.9 (8.7)] and no differences were found in ARFS between urban and rural BCS. This is the first study dedicated exclusively to describing the diet quality of Australian BCS. Although no difference was found when comparisons were made with a HC group, there is considerable room for improvement in the diet quality of Australian BCS. Given research suggesting higher risk of chronic conditions such as obesity amongst BCS, and the recognition of optimising diet quality as a key factor in health promotion for all population groups, data from the present study suggest the need for research targeting the feasibility and impact of improving diet quality of Australian BCS.


Assessing the variability in transmission of bovine tuberculosis within Spanish cattle herds.
In Spain, despite years of efforts to eradicate bovine tuberculosis (bTB), the disease is still endemic, with some areas of high prevalence. In this context, the surveillance and control plans may need to be re-evaluated, and understanding the dynamics of bTB spread within Spanish herds may help to develop new strategies for reducing the time for detection of infected herds and for the elimination of bTB from the herds already infected. Here, we developed a compartmental stochastic model to simulate bTB within-herd transmission, fed it with epidemiological data from 22 herds (obtained from a previous work) and carried out parameter inference using Approximate Bayesian Computing methods We also estimated the "Within-herd transmission potential Number" (Rh), i.e. the average number of secondary cases generated by a single animal infected introduced into a totally susceptible herd, considering different scenarios depending on the frequency of controls. The median global values obtained for the transmission parameters were: for the transmission coefficient (β), 0.014 newly infected animals per infectious individual per day (i.e. 5.2 per year), for the rate at which infected individuals become infectious (α), 0.01 per day (equivalent to a latent period of 97 days), and for the rate at which infected individuals become reactive to the skin test (α1), 0.08 per day (equivalent to a period of 12 days for an infected animal to become reactive). However, the results also evidenced a great variability in the estimates of those parameters (in particular β and α) among the 22 herds. Considering a 6-month interval between tests, the mean Rh was 0.23, increasing to 0.82 with an interval of 1 year, and to 2.01 and 3.47 with testing intervals of 2 and 4 years, respectively.


Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid.
We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection: concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.


Democratizing economics: pluralism as a path toward sustainability.
Climate scientists point to a number of unsustainable trends concerning the environment and natural resources. There is also ongoing concern about poverty reduction, labor rights, and other social aspects of sustainable development. Growing numbers argue that change is required, but still at issue is the extent of change and how to facilitate it. In this paper, the focus is on the dominant interpretive schema of influential actors with respect to ideas about science in society, paradigms in economics, and ideological orientations. The authors argue that the monopolistic position of neoclassical economics at university departments of economics in different parts of the world, and the spread of its associated technocratic logic within broader policy arenas, should be abandoned in favor of a more ideologically open attitude that facilitates discussion and debate within academia, public policy, and in civil society more generally. In a sense, economics requires "democratization" with implications for approaches to sustainability monitoring, accounting, and the assessment of projects and policies. The paper provides suggestions for developing sustainability assessment technologies and practices that take pluralism seriously.


The influence of red on perceptions of relative dominance and threat in a competitive context.
Recent research has revealed that a person or team wearing red is more likely to win a physical contest than a person or team wearing another color. In the present research, we examined whether red influences perceptions of relative dominance and threat in an imagined same-sex competitive context, and did so attending to the distinction between wearing red oneself and viewing red on an opponent. Results revealed a bidirectional effect: wearing red enhanced perceptions of one's relative dominance and threat, and viewing an opponent in red enhanced perceptions of the opponent's relative dominance and threat. These effects were observed across sex, and participants seemed unaware of the influence of red on their responses. Our findings lead to practical suggestions regarding the use of colored attire in sport contexts, and add to an emerging, provocative literature indicating that red has a subtle but important influence on psychological functioning.


The development and validation of a more discriminating functional hip score for research.
Total hip arthroplasty (THA) is a commonly performed procedure with increasing frequency in the young adult. While most available outcome measures can document postoperative improvement in pain and function, they do not measure the ability to perform high-demand activities. We present and validate a user-friendly discriminating hip scoring system (the functional hip score) for use in younger, "high-demand" patients undergoing hip arthroplasty surgery. We studied 38 subjects without any hip symptoms and 72 patients undergoing THA for osteoarthritis of the hip. Preprocedure and postprocedure scores were collected in the latter cohort of patients. SF-36 and WOMAC scores were used to validate our functional scoring system. The functional hip score was tested for internal consistency, reliability, and criterion validity. The functional hip score had high test-retest reliability, internal consistency, and criterion validity. This can be used to measure functional outcome in the younger high-demand adult patient undergoing THA. Our discriminating functional hip score can reliably measure improvement in hip function in the younger high-demand adult. Current scoring systems have ceiling effects and are unable to differentiate a high performing hip replacement from the routine hip replacement. The use of functional tasks that are measured objectively allows better documentation of improvement in hip function.


Humanized archaeal ferritin as a tool for cell targeted delivery.
Human ferritins have been extensively studied to be used as nanocarriers for diverse applications and could represent a convenient alternative for targeted delivery of anticancer drugs and imaging agents. However, the most relevant limitation to their applications is the need for highly acidic experimental conditions during the initial steps of particle/cargo assembly, a process that could affect both drug stability and the complete reassembly of the ferritin cage. To overcome this issue the unique assembly of Archaeoglobus fulgidus ferritin was genetically engineered by changing a surface exposed loop of 12 amino acids connecting B and C helices to mimic the sequence of the analogous human H-chain ferritin loop. This new chimeric protein was shown to maintain the unique, cation linked, association-dissociation properties of Archaeoglobus fulgidus ferritin occurring at neutral pH values, while exhibiting the typical human H-homopolymer recognition by the transferrin receptor TfR1. The chimeric protein was confirmed to be actively and specifically internalized by HeLa cells, thus representing a unique nanotechnological tool for cell-targeted delivery of possible payloads for diagnostic or therapeutic purposes. Moreover, it was demonstrated that the 12 amino acids' loop is necessary and sufficient for binding to the transferrin receptor. The three-dimensional structure of the humanized Archaeoglobus ferritin has been obtained both as crystals by X-ray diffraction and in solution by cryo-EM.


Clinical practice guidelines on the use of integrative therapies as supportive care in patients treated for breast cancer.
The majority of breast cancer patients use complementary and/or integrative therapies during and beyond cancer treatment to manage symptoms, prevent toxicities, and improve quality of life. Practice guidelines are needed to inform clinicians and patients about safe and effective therapies. Following the Institute of Medicine's guideline development process, a systematic review identified randomized controlled trials testing the use of integrative therapies for supportive care in patients receiving breast cancer treatment. Trials were included if the majority of participants had breast cancer and/or breast cancer patient results were reported separately, and outcomes were clinically relevant. Recommendations were organized by outcome and graded based upon a modified version of the US Preventive Services Task Force grading system. The search (January 1, 1990-December 31, 2013) identified 4900 articles, of which 203 were eligible for analysis. Meditation, yoga, and relaxation with imagery are recommended for routine use for common conditions, including anxiety and mood disorders (Grade A). Stress management, yoga, massage, music therapy, energy conservation, and meditation are recommended for stress reduction, anxiety, depression, fatigue, and quality of life (Grade B). Many interventions (n = 32) had weaker evidence of benefit (Grade C). Some interventions (n = 7) were deemed unlikely to provide any benefit (Grade D). Notably, only one intervention, acetyl-l-carnitine for the prevention of taxane-induced neuropathy, was identified as likely harmful (Grade H) as it was found to increase neuropathy. The majority of intervention/modality combinations (n = 138) did not have sufficient evidence to form specific recommendations (Grade I). Specific integrative therapies can be recommended as evidence-based supportive care options during breast cancer treatment. Most integrative therapies require further investigation via well-designed controlled trials with meaningful outcomes.


Serial analysis of imaging parameters in patients with newly diagnosed glioblastoma multiforme.
The objective of this study was to test the predictive value of serial MRI data in relation to clinical outcome for patients with glioblastoma multiforme (GBM). Sixty-four patients with newly diagnosed GBM underwent conventional MRI and diffusion-weighted and perfusion-weighted imaging postsurgery and prior to radiation/chemotherapy (pre-RT), immediately after RT (post-RT), and every 1-2 months thereafter until tumor progression, up to a maximum of 1 year. Tumor volumes and perfusion and diffusion parameters were calculated and subject to time-independent and time-dependent Cox proportional hazards models that were adjusted for age and MR scanner field strength. Larger volumes of the T2 hyperintensity lesion (T2ALL) and nonenhancing lesion (NEL) at pre-RT, as well as increased anatomic volumes at post-RT, were associated with worse overall survival (OS). Higher normalized cerebral blood volumes (nCBVs), normalized peak height (nPH) and normalized recirculation factors (nRF) at pre-RT, and nCBV at post-RT, in the T2ALL and NEL, were associated with shorter progression-free survival (PFS). From pre- to post-RT, there was a reduction in nCBV and nPH and an increase in apparent diffusion coefficient (ADC). Patients with lower nRF values at pre-RT, or a larger increase in nRF from pre-RT to post-RT, had significantly longer PFS. Time-dependent analysis showed that patterns of changes in ADC and anatomic volumes were associated with OS, while changes in nCBV, nPH, and the contrast-enhancing volume were associated with PFS. Our studies suggest that quantitative MRI variables derived from anatomic and physiological MRI provide useful information for predicting outcome in patients with GBM.


Host Plant Resistance as an Alternative to Methyl Bromide for Managing Meloidogyne incognita in Pepper.
Pre-plant soil fumigation with methyl bromide and host resistance were compared for managing the southern root-knot nematode (Meloidogyne incognita) in pepper. Three pepper cultivars (Carolina Cayenne, Keystone Resistant Giant, and California Wonder) that differed in resistance to M. incognita were grown in field plots that had been fumigated with methyl bromide (98% CHBr : 2% CClNO [w/w]) before planting or left untreated. Carolina Cayenne is a well-adapted cayenne-type pepper that is highly resistant to M. incognita. The bell-type peppers Keystone Resistant Giant and California Wonder are intermediate to susceptible and susceptible, respectively. None of the cultivars exhibited root galling in the methyl bromide fumigated plots and nematode reproduction was minimal (<250 eggs/g fresh root), indicating that the fumigation treatment was highly effective in controlling M. incognita. Root galling of Carolina Cayenne and nematode reproduction were minimal, and fruit yields were not reduced in the untreated plots. The root-galling reaction for Keystone Resistant Giant was intermediate (gall index = 2.9, on a scale of 1 to 5), and nematode reproduction was moderately high. However, yields of Keystone Resistant Giant were not reduced in untreated plots. Root galling was severe (gall index = 4.3) on susceptible California Wonder, nematode reproduction was high, and fruit yields were reduced (P </= 0.05) in untreated plots. The resistance exhibited by Carolina Cayenne and Keystone Resistant Giant provides an alternative to methyl bromide for reducing yield losses by southern root-knot nematodes in pepper. The high level of resistance of Carolina Cayenne also suppresses population densities of M. incognita.


The use of new and better antibiotics for bacterial infections in patients with leukemia.
Bacterial infection is the most common complication of chemotherapy-induced neutropenia particularly in patients with hematologic malignancies. Bacterial infections predominate during the initial phases of neutropenic episodes. The spectrum of bacterial infection continues to evolve globally and locally at the institutional level, as do patterns of antimicrobial susceptibility/resistance. These trends are often associated with local treatment practices (eg, use of antimicrobial prophylaxis, open versus restricted formularies, clinical pathways and/or guidelines) and have a significant effect on the nature of empiric antimicrobial therapy. Increasing rates of resistance among gram-positive and gram-negative bacteria are posing new therapeutic challenges. These challenges can to some extent be overcome by new drug development. Many novel agents for the treatment of resistant gram-positive infections have been developed and are being evaluated in clinical trials. Newer agents for the treatment of Clostridium difficile associated diarrhea are also in the pipeline. Far fewer options to treat multi-drug resistant gram-negative infections exist, and new drug development is lagging behind. Consequently, the judicious use of currently available agents is essential. This is best achieved by the development of multidisciplinary antibiotic stewardship teams that gather baseline data, make recommendations for appropriate antimicrobial usage, and provide monitoring and feedback services to clinical care providers. Along with strict adherence to infection control policies, antimicrobial stewardship provides the best strategies for the management of infectious complications in patients with hematologic malignancies and other high-risk settings.


Physical condition, longevity, and social performance of Dutch haemophiliacs, 1972-85.
A study was carried out among haemophiliacs in The Netherlands to evaluate the effect of modern substitution treatment (replacing the missing clotting factors) on medical and social performance. Three questionnaires were sent between 1972 and 1985. The use of prophylactic treatment in the group of patients with severe and moderately severe haemophilia increased from 21% (n = 242) in 1972 to 36% (n = 559) in 1985. Home treatment programmes increased from 4% to 53%. Overall mortality was 2.1 times higher than in the general male population, which leads to a calculated life expectancy of 66 years compared with 74 years in the general male population. Severe joint impairment was prominent in the older age groups, reflecting insufficient treatment in the past. A sharp decrease in the use of inpatient and outpatient hospital facilities was observed as well as much less absence from school and work. It is concluded that the high costs of modern substitution treatment are fully justified.


Optical control of NMDA receptors with a diffusible photoswitch.
N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform, but can be converted into its active cis-isoform using one-photon (near UV) or two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates ATG within milliseconds, allowing agonist removal on the timescale of NMDAR deactivation. ATG is compatible with Ca(2+) imaging and can be used to optically mimic synaptic coincidence detection protocols. Thus, ATG can be used like traditional caged glutamate compounds, but with the added advantages of NMDAR specificity, low antagonism of GABAR-mediated currents, and precise temporal control of agonist delivery.


A recombinant human adenovirus vaccine against rabies.
Rabies continues to be a serious problem in both developed and developing nations due to the reservoir of rabies virus in wildlife vectors. The control and worldwide eradication of rabies depends on the development of safe, effective, and economical vaccines that might be used in preexposure vaccination programs for humans and animals. To this end an infectious human adenovirus type 5 recombinant virus that contains the rabies glycoprotein gene, and which may serve as the prototype for a new class of vaccines against rabies, was constructed and tested. This recombinant, when administered by either the parenteral or oronasal route, was highly effective in eliciting good levels of rabies-neutralizing antibodies in the sera of dogs and mice. Mice immunized by the recombinant virus were protected from lethal intracerebral challenge with rabies virus.


Feasibility of using computer-tailored and internet-based interventions to promote physical activity in underserved populations.
Computer-tailored and Internet-based interventions to promote physical activity behavior have shown some promise, but only few have been tested among African Americans. We examined the feasibility and efficacy of three 1-year, multiple contact physical activity interventions (Tailored Internet, Tailored Print, Standard Internet) in a subsample of African American participants (n = 38) enrolled in a randomized controlled trial. Participants randomly assigned to Tailored Internet and Print programs received individually tailored computer expert system feedback delivered via Internet or print. Participants in the Standard Internet program received access to six currently available physical activity Web sites. Self-reported physical activity was assessed at baseline and 6 and 12 months with the 7-Day Physical Activity Recall. Across all participants, physical activity changed from 17.24 min/week (standard deviation [SD] = 20.72) at baseline to 139.44 min/week (SD = 99.20) at 6 months, to 104.26 min/week (SD = 129.14) at 12 months. According to available consumer satisfaction data (n = 30), 70% reported reading most or all of the physical activity information received by Internet or mail. Most participants described the Internet- and print-based physical activity programs as "somewhat" or "very" helpful (80%) and enjoyable (87%). These findings suggest that computer-tailored and Internet-based interventions are able to produce long-term increases in physical activity and associated process variables among African American participants. Future studies with larger numbers of African American participants are needed to determine which of the programs (Tailored Print, Tailored Internet, Standard Internet) are more effective and what program modifications might be helpful in assisting this population in becoming more active.


MetaRanker 2.0: a web server for prioritization of genetic variation data.
MetaRanker 2.0 is a web server for prioritization of common and rare frequency genetic variation data. Based on heterogeneous data sets including genetic association data, protein-protein interactions, large-scale text-mining data, copy number variation data and gene expression experiments, MetaRanker 2.0 prioritizes the protein-coding part of the human genome to shortlist candidate genes for targeted follow-up studies. MetaRanker 2.0 is made freely available at www.cbs.dtu.dk/services/MetaRanker-2.0.