Applications of natural products in the control of mosquito-transmitted diseases

Mosquito-transmitted diseases remain one of the most significant causes of mortality in the African continent, despite successes in controlling these diseases in other regions of the world. The disproportionate impact in areas of poverty suggests a need for control that is efficient and does notrequire complex technological control strategies. Focusing on the vectors of disease, the mosquito, there are many alternatives to synthetic, chemical pesticides that await discovery and development. Although some natural products have been described, there is still a need for continuing research that incorporates endogenous knowledge in the selection process for potential vector control candidates. Recent experiments using natural products are summarized. Ultimately, a paradigm shift in research that evaluates natural products in a comparative manner will help to produce new materials for effective and efficient control of vectors and thereby achieve sustainable reduction of the impacts from the diseases they carry

Assessing Descriptive Substance in Free-Text Collection-Level Metadata

Collection-level metadata has the potential to provide important information about the features and purpose of individual collections. This paper reports on a content analysis of collection records in an aggregation of cultural heritage collections. The findings show that the free-text Description field often provides more accurate and complete representation of subjects and object types than the specified fields. Properties such as importance, uniqueness, comprehensiveness, provenance, and creator are articulated, as well as other vital contextual information about the intentions of a collector and the value of a collection, as a whole, for scholarly users. The results demonstrate that the semantically rich free-text Description field is essential to understanding the context of collections in large aggregations and can serve as a source of data for enhancing and customizing controlled vocabulariesIMLS NLG Research and Demonstration grant LG-06-07-0020-07published or submitted for publicationis peer reviewe

Dublin Core Metadata Harvested Through OAI-PMH

The introduction in 2001 of the Open Archives Initiative Protocol for Metadata Harvesting (OAI-PMH) increased interest in and awareness of metadata quality issues relevant to digital library interoperability and the use of harvested metadata to build "union catalogs" of digital information resources. Practitioners have offered wide-ranging advice to metadata authors and have suggested metrics useful for measuring the quality of shareable metadata. Is there evidence of changes in metadata practice in response to such advice and/or as a result of an increased awareness of the importance of metadata interoperability? This paper looks at metadata records created over a six-year period that have been harvested by the University of Illinois at Urbana Champaign, and reports on quantitative and qualitative analyses of changes observed over time in shareable metadata quality.IMLS National Leadership Grant LG-02-02-0281published or submitted for publicationis peer reviewe

Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

Early tumor response to intraarterial or intravenous administration of carboplatin to treat naturally occurring lower urinary tract carcinoma in dogs.

BackgroundSurvival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.ObjectiveTo describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).AnimalsClient-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).MethodsRetrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.ResultsIntraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).Conclusion and clinical importanceThis study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined

Acute effects of exercise on appetite, ad libitum energy intake and appetite-regulatory hormones in lean and overweight/obese men and women

Background: Acute exercise does not elicit compensatory changes in appetite parameters in lean individuals; however, less is known about responses in overweight individuals. This study compared the acute effects of moderate-intensity exercise on appetite, energy intake and appetite-regulatory hormones in lean and overweight/obese individuals. Methods: Forty-seven healthy lean (n=22, 11 females; mean (s.d.) 37.5 (15.2) years; 22.4 (1.5) kg m−2) and overweight/obese (n=25, 11 females; 45.0 (12.4) years, 29.2 (2.9) kg m−2) individuals completed two, 8 h trials (exercise and control). In the exercise trial, participants completed 60 min treadmill exercise (59 (4)% peak oxygen uptake) at 0–1 h and rested thereafter while participants rested throughout the control trial. Appetite ratings and concentrations of acylated ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured at predetermined intervals. Standardised meals were consumed at 1.5 and 4 h and an ad libitum buffet meal was provided at 7 h. Results: Exercise suppressed appetite (95% confidence interval (CI) −3.1 to −0.5 mm, P=0.01), and elevated delta PYY (95% CI 10 to 17 pg ml−1, P<0.001) and GLP-1 (95% CI 7 to 10 pmol l−1, P<0.001) concentrations. Delta acylated ghrelin concentrations (95% CI −5 to 3 pg ml−1, P=0.76) and ad libitum energy intake (95% CI −391 to 346 kJ, P=0.90) were similar between trials. Subjective and hormonal appetite parameters and ad libitum energy intake were similar between lean and overweight/obese individuals (Pgreater than or equal to0.27). The exercise-induced elevation in delta GLP-1 was greater in overweight/obese individuals (trial-by-group interaction P=0.01), whereas lean individuals exhibited a greater exercise-induced increase in delta PYY (trial-by-group interaction P<0.001). Conclusions: Acute moderate-intensity exercise transiently suppressed appetite and increased PYY and GLP-1 in the hours after exercise without stimulating compensatory changes in appetite in lean or overweight/obese individuals. These findings underscore the ability of exercise to induce a short-term energy deficit without any compensatory effects on appetite regardless of weight status

Earthquake distribution patterns in Africa: their relationship to variations in lithospheric and geological structure, and their rheological implications

We use teleseismic waveform inversion, along with depth phase analysis, to constrain the centroid depths and source parameters of large African earthquakes. The majority of seismic activity is concentrated along the East African Rift System, with additional active regions along stretches of the continental margins in north and east Africa, and in the Congo Basin. We examine variations in the seismogenic thickness across Africa, based on a total of 227 well-determined earthquake depths, 112 of which are new to this study. Seismogenic thickness varies in correspondence with lithospheric thickness, as determined from surface wave tomography, with regions of thick lithosphere being associated with seismogenic thicknesses of up to 40 km. In regions of thin lithosphere, the seismogenic thickness is typically limited to ≤20 km. Larger seismogenic thicknesses also correlate with regions that have dominant tectonothermal ages of ≥1500 Ma, where the East African Rift passes around the Archean cratons of Africa, through the older Proterozoic mobile belts. These correlations are likely to be related to the production, affected by method and age of basement formation, and preservation, affected by lithospheric thickness, of a strong, anhydrous lower crust. The Congo Basin contains the only compressional earthquakes in the continental interior. Simple modelling of the forces induced by convective support of the African plate, based on long-wavelength free-air gravity anomalies, indicates that epeirogenic effects are sufficient to account for the localization and occurrence of both extensional and compressional deformation in Africa. Seismicity along the margins of Africa reflects a mixture between oceanic and continental seismogenic characteristics, with earthquakes in places extending to 40 km depth

Sound field planarity characterized by superdirective beamforming

The ability to replicate a plane wave represents an essential element of spatial sound field reproduction. In sound field synthesis, the desired field is often formulated as a plane wave and the error minimized; for other sound field control methods, the energy density or energy ratio is maximized. In all cases and further to the reproduction error, it is informative to characterize how planar the resultant sound field is. This paper presents a method for quantifying a region's acoustic planarity by superdirective beamforming with an array of microphones, which analyzes the azimuthal distribution of impinging waves and hence derives the planarity. Estimates are obtained for a variety of simulated sound field types, tested with respect to array orientation, wavenumber, and number of microphones. A range of microphone configurations is examined. Results are compared with delay-and-sum beamforming, which is equivalent to spatial Fourier decomposition. The superdirective beamformer provides better characterization of sound fields, and is effective with a moderate number of omni-directional microphones over a broad frequency range. Practical investigation of planarity estimation in real sound fields is needed to demonstrate its validity as a physical sound field evaluation measure. © 2013 Acoustical Society of America

Deubiquitylating enzymes and drug discovery: emerging opportunities

More than a decade after a Nobel Prize was awarded for the discovery of the ubiquitin-proteasome system and clinical approval of proteasome and ubiquitin E3 ligase inhibitors, first-generation deubiquitylating enzyme (DUB) inhibitors are now approaching clinical trials. However, although our knowledge of the physiological and pathophysiological roles of DUBs has evolved tremendously, the clinical development of selective DUB inhibitors has been challenging. In this Review, we discuss these issues and highlight recent advances in our understanding of DUB enzymology and biology as well as technological improvements that have contributed to the current interest in DUBs as therapeutic targets in diseases ranging from oncology to neurodegeneration.The authors thank L. Greger for the generation of the phylogenic tree. Research in the S.P.J. laboratory is funded by the Cancer Research UK (CRUK) Program Grant C6/A18796 and a Wellcome Trust Investigator Award (206388/Z/17/Z), and institute core infrastructure funding is provided by the CRUK (C6946/A24843) and the Wellcome Trust (WT203144)