Behavioral and anatomical characterization of the bilateral sciatic nerve chronic constriction (bCCI) injury: correlation of anatomic changes and responses to cold stimuli

<p>Abstract</p> <p>Background</p> <p>Unilateral constrictive sciatic nerve injury (uCCI) is a common neuropathic pain model. However, the bilateral constrictive injury (bCCI) model is less well studied, and shows unique characteristics. In the present study, we sought to correlate effects of bCCI on nocifensive responses to cold and mechanical stimuli with selected dorsal horn anatomic markers. bCCI or sham ligation of both rat sciatic nerves were followed up to 90 days of behavioural testing. Additional rats sacrificed at 15, 30 and 90 days were used for anatomic analyses. Behavioural tests included hindpaw withdrawal responses to topical acetone, cold plate testing, an operant thermal preference task and hindpaw withdrawal thresholds to mechanical probing.</p> <p>Results</p> <p>All nocifensive responses to cold increased and remained enhanced for >45 days. Mechanical withdrawal thresholds decreased for 25 days only. Densitometric analyses of immunoperoxidase staining in the superficial dorsal horn at L4-5 revealed decreased cholecystokinin (CCK) staining at all times after bCCI, decreased mu opiate receptor (MOR) staining, maximal at 15 days, increased neuropeptide Y (NPY) staining only at days 15 and 30, and increased neurokinin-1 receptor (NK-1R) staining at all time points, maximal at 15 days. Correlation analyses at 45 days post-bCCI, were significant for individual rat nocifensive responses in each cold test and CCK and NK-1R, but not for MOR or NPY.</p> <p>Conclusions</p> <p>These results confirm the usefulness of cold testing in bCCI rats, a new approach using CCI to model neuropathic pain, and suggest a potential value of studying the roles of dorsal horn CCK and substance P in chronic neuropathic pain. Compared to human subjects with neuropathic pain, responses to cold stimuli in rats with bCCI may be a useful model of neuropathic pain.</p

Effects of Fish Restoration Practices on Amphibians in Yellowstone National Park, Wyoming

Throughout the Western United States, fisheries managers are attempting to restore native cutthroat trout (Onchorynchus clarkii) populations by removing nonnative fish species. A new formulation of the EPA approved piscicide rotenone (CFT Legumine) is increasingly being used as a method to accomplish this removal. Because fish restoration projects bring about an abrupt change to aquatic environments, it is important to consider their immediate and long-term effects on non-target species, such as amphibians. We assessed the effects of fish removal on amphibians in Yellowstone National Park (YNP) by investigating the toxicity of rotenone to and the long-term impacts of removing fish on local amphibian populations. CFT Legumine (5% rotenone) was applied to High Lake in YNP (2006) to remove stocked Yellowstone cutthroat trout (O. c. bouvieri). To determine toxicity, amphibian surveys were conducted immediately prior to the treatment to obtain pre-treatment tadpole population estimates. Post-treatment surveys were conducted both immediately, for assessing treatment-related mortality (during and after application), and 1, 2, and 3 years following to obtain tadpole abundance estimates in the years after application and to address the long-term effects of fish removal and reintroduction. The results of the toxicity trials revealed that in the 24 hrs following application, rotenone was lethal to gill-breathing amphibian tadpoles and nonlethal to non-gill breathing metamorphs, juveniles, and adults. In the years following, tadpole repopulation occurred at levels above the pre-treatment abundance estimate, though both tadpole abundance and distribution appeared correlated with fish presence

Observation of coupled plasmon-polariton modes of plasmon waveguides for electromagnetic energy transport below the diffraction limit

We investigate the possibility of using arrays of closely spaced metal nanoparticles as plasmon waveguides for electromagnetic energy below the diffraction limit of light. Far-field spectroscopy on arrays of closely spaced 50 nm Au particles fabricated using electron beam lithography reveals the presence of near-field optical particle interactions that lead to shifts in the plasmon resonance frequencies for longitudinal and transverse excitations. We link this observation to a point-dipole model for energy transfer in plasmon waveguides and give an estimate of the expected group velocities and energy decay lengths for the fabricated structures. A near-field optical excitation and detection scheme for energy transport is proposed and demonstrated. The fabricated structures show a high propagation loss of about 3 dB / 15 nm which renders a direct experimental observation of energy transfer impossible. The nature of the loss and ways to decrease it by an order of magnitude are discussed. We also present finite-difference time-domain simulations on the energy transfer properties of plasmon waveguides

Meta-signature of human endometrial receptivity : a meta-analysis and validation study of transcriptomic biomarkers

Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up-and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from 'pre-receptive' and 88 from mid-secretory, 'receptive' phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.Peer reviewe

Methicillin-Resistant Staphylococcus aureus in a Beauty Salon, the Netherlands

An outbreak of community-associated USA300 methicillin-resistant Staphylococcus aureus occurred in a beautician and 2 of her customers. Eight other persons, who were either infected (n = 5) or colonized (n = 3), were linked to this outbreak, including a family member, a household contact, and partners of customers

Linking Adult Reproduction and Larval Density of Invasive Carp in a Large River

Identifying how temporal variation in the environment affects reproductive success of invasive alien species will aid in predicting future establishment and tracking dynamics of established populations. Asian carp Hypophthalmichthys spp. have become a nuisance in recent years in the Mississippi River basin. Their populations are apparently expanding, indicating favorable conditions for reproduction. During 2004 and 2005, we quantified mean density of Asian carp larvae, mean monthly gonadosomatic index (GSI) of adult males and females, and number of eggs within mature females in the lower Illinois River, a major tributary of the Mississippi River. A flood (water velocity ≥ 0.7 m/s) and drought (\u3c0.2 m/s) occurred during apparent spawning in 2004 and 2005, respectively. During 2004, Asian carp larvae were found during 32% of sampling weeks; mean GSI and fecundity were relatively low for adults, probably reflecting partially spawned individuals and perhaps low reproductive investment. During the drought of 2005, larval stages were present during only one (5%) of the sampling weeks, whereas mean GSI and fecundity of adults were high through summer. Females resorbed their eggs instead of spawning during this year. Spawning conditions during low water periods appear to be unsuitable for Asian carps, inhibiting adult spawning and yielding few larvae. Spawning conditions during 2004 were better but still yielded low densities of larvae relative to native fishes. Reproduction in the lower Illinois River appears to be linked to river flow and its impact on adult spawning decisions, but conditions for strong year-class production (i.e., high larval densities) may be rarer than previously expected

Plasma proteome profiling identifies changes associated to AD but not to FTD

Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 +/- 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 +/- 7.9; 45% female), AD patients (n = 57; age = 65.5 +/- 8.0; 39% female), and non-demented controls (n = 148; 61.3 +/- 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 +/- 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 +/- 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 +/- 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts

Movement and Habitat Selection by Invasive Asian Carps in a Large River

We evaluated the habitat use and movements of 50 adult bighead carp Hypophthalmichthys nobilis and 50 silver carp H. molitrix by means of ultrasonic telemetry during spring–summer 2004 and 2005 to gain insight into the conditions that facilitate their establishment, persistence, and dispersal in the lower Illinois River (river kilometer 0–130). Movement and habitat use were monitored with stationary receivers and boat-mounted tracking. The relative availability of four macrohabitat categories (main channel, island side channel, channel border, and connected backwater) was quantified to determine selection; discriminant function analysis was used to evaluate changes in physical characteristics within each category. A flood pulse occurred in spring through early summer of 2004 but not 2005. Movement rates (km/week) of both species were positively correlated with flow but not with temperature. Including data from stationary receivers greatly increased estimates of daily movement. During low summer flow, both species typically selected channel borders and avoided the main channel and backwaters. Both species rarely occupied depths over 4 m, regardless of abiotic conditions. Flood pulses appear to trigger dispersal, while habitat use is only specific during low summer flow. Thus, movement prevention efforts (e.g., dispersal barriers) will require particular vigilance during late-winter or spring flooding, and controlled removal (e.g., harvest) should be directed toward selected habitats during summer

Dengue viruses cluster antigenically but not as discrete serotypes.

The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.This research was supported in part by the Intramural Research Program of the US NIH, National Institute of Allergy and Infectious Diseases, European Union (EU) FP7 programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science Program (HFSP) program grant P0050/2008, the NIH Director’s Pioneer Award DP1-OD000490-01, the FIRST program from the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (E.H.). The antigenic cartography toolkit was in part supported by NIAID-NIH Centers of Excellence for Influenza Research and Surveillance contracts HHSN266200700010C and HHSN272201400008C for use on influenza virus. L.C.K. was supported by the Gates Cambridge Scholarship and the NIH Oxford Cambridge Scholars Program. J.M.F. was supported by an MRC Fellowship (MR/K021885/1) and a Junior Research Fellowship from Homerton College Cambridge. E.C.H. was supported by an NHMRC Australia Fellowship. N.V. and R.B.T were supported by NIH contract HHSN272201000040I/HHSN27200004/D04.This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aac501