TRSP is dispensable for the Plasmodium pre-erythrocytic phase

Plasmodium sporozoites deposited in the skin following a mosquito bite must migrate and invade blood vessels to complete their development in the liver. Once in the bloodstream, sporozoites arrest in the liver sinusoids, but the molecular determinants that mediate this specific homing are not yet genetically defined. Here we investigate the involvement of the thrombospondin-related sporozoite protein (TRSP) in this process using knockout Plasmodium berghei parasites and in vivo bioluminescence imaging in mice. Resorting to a homing assay, trsp knockout sporozoites were found to arrest in the liver similar to control parasites. Moreover, we found no defects in the establishment of infection in mice following inoculation of trsp knockout sporozoites via intravenous and cutaneous injection or mosquito bite. Accordingly, mutant sporozoites were also able to successfully invade hepatocytes in vitro. Altogether, these results suggest TRSP may have a redundant role in the completion of the pre-erythrocytic phase of the malaria parasite. Nonetheless, identifying molecules with paramount roles in this phase could aid in the search for new antigens needed for the design of a protective vaccine against malaria.We would like to thank: Prof. Anabela Cordeiro da Silva from the IBMC/i3S for the exceptional hosting conditions; Dr. Ana Xavier Carvalho from the IBMC/i3S for the critical reading of the manuscript; the team of the CEPIA from Institut Pasteur, Paris, for providing the Anopheles stephensi female mosquitos. The following reagents were obtained through BEI Resources, NIAID, NIH: (a) Plasmid pL0001, for Transfection in Plasmodium berghei, MRA-770, contributed by Andrew P. Waters; (b) Hybridoma 3D11 Anti-Plasmodium berghei 44-Kilodalton Sporozoite Surface Protein (Pb44), MRA-100, contributed by Victor Nussenzweig. This work was supported by funds from project Norte-01-0145-FEDER-000012 - Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through FEDER. This work also received funds from the Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência (MEC) co-funded by FEDER (EXPL/JTAVARES-IF/00881/2012/CP0158/CT0005,EXPL/IMI-MIC/1331/ 2013) under the Partnership agreement PT2020, through the Research Unit No. 4293. J.T. is an Investigator FCT funded by National funds through FCT and co-funded through European Social Fund within the Human Potential Operating Programme. D.M.C., M.S. and A.R.T. are funded by FCT individual fellowships SFRH/ BD/123734/2016, SFRH/BD/133485/2017 and SFRH/BD/133276/2017 respectively). The authors acknowledge the support of the BioSciences Screening i3S Scientific Platform, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)

Aeolian features on Venus: Preliminary Magellan results

Magellan synthetic aperture radar data reveal numerous surface features that are attributed to aeolian, or wind processes. Wind streaks are the most common aeolian feature. They consist of radar backscatter patterns that are high, low, or mixed in relation to the surface on which they occur. A data base of more than 3400 wind streaks shows that low backscatter linear forms (long, narrow streaks) are the most common and that most streaks occur between 17°S to 30°S and 5°N to 53°N on smooth plains. Moreover, most streaks are associated with deposits from certain impact craters and some tectonically deformed terrains. We infer that both of these geological settings provide fine particulate material that can be entrained by the low-velocity winds on Venus. Turbulence and wind patterns generated by the topographic features with which many streaks are associated can account for differences in particle distributions and in the patterns of the wind streaks. Thus, some high backscatter streaks are considered to be zones that are swept free of sedimentary particles to expose rough bedrock; other high backscatter streaks may be lag deposits of dense materials from which low-density grains have been removed (dense materials such as ilmenite or pyrite have dielectric properties that would produce high backscatter patterns). Wind streaks generally occur on slopes < 2° and tend to be oriented toward the equator, consistent with the Hadley model of atmospheric circulation. In addition to wind streaks, other aeolian features on Venus include yardangs(?) and dune fields. The Aglaonice dune field, centered at 25°S, 340°E, covers ∼1290 km^2 and is located in an ejecta flow channel from the Aglaonice impact crater. The Meshkenet dune field, located at 67°N, 90°E, covers ∼17,120 km^2 in a valley between Ishtar Terra and Meshkenet Tessera. Wind streaks associated with both dune fields suggest that the dunes are of transverse forms in which the dune crests are perpendicular to the prevailing winds. Dunes on Venus signal the presence of sand-size (∼60 to 2,000 μm) grains. The possible yardangs are found at 9°N, 60.5°E, about 300 km southeast of the crater Mead. Although most aeolian features are concentrated in smooth plains near the equator, the occurrence of wind streaks is widespread, and some have been found at all latitudes and elevations. They demonstrate that aeolian processes operate widely on Venus. The intensity of wind erosion and deposits, however, varies with locality and is dependent on the wind regime and supply of particles

Internal transport of alien and native plants by geese and ducks: An experimental study

© 2015 John Wiley & Sons Ltd. Summary: Alien plant species are rapidly spreading in aquatic ecosystems around the world, causing major ecological effects. They are typically introduced by humans, after which natural vectors facilitate their further spread. Migratory waterbirds have long been recognised as important dispersal vectors for native and aquatic plants, yet little is known about their role in the spread of alien species. We determined experimentally the potential for long-distance dispersal of native and alien wetland plants in Europe by two abundant waterfowl: mallards Anas platyrhynchos and greylag geese Anser anser. We fed seeds from two plants alien to Europe and two native plants to 10 individuals of each bird species, testing for the effects of bird and plant species on the potential for dispersal. Intact seeds were retrieved from faeces for up to 4 days after ingestion. The proportion of seeds retrieved intact varied significantly between plant, but not bird, species. Retrieval was highest for the invasive water primrose Ludwigia grandiflora (>35% of ingested seeds), lowest for the invasive cordgrass Spartina densiflora (<3%) and intermediate for the native glasswort Arthrocnemum macrostachyum and seablite Suaeda vera (5-10%). Seed retrieval patterns over time varied between both plant and bird species. Contrary to expectations, seeds were retained in the gut for longer in the smaller mallards. No Spartina seeds germinated after retention for over 8 h, whereas some seeds of the other species germinated even after retention for 72 h. Germinability was reduced by gut passage for Ludwigia and Arthrocnemum seeds. Ludwigia seeds recovered from geese were more likely to germinate than those recovered from mallards. Time to germination was reduced by gut passage for Spartina and Ludwigia, but increased with retention time. Ducks and geese evidently have the potential for long-distance transport of alien and native plant seeds, with maximal dispersal distances of well over 1000 km. The much greater potential of Ludwigia than Spartina for dispersal by waterfowl is consistent with its faster expansion across Europe. Maximum retention times of wetland seeds have been underestimated in previous experimental studies that lasted only 1-2 days. Contrary to previous studies, wetland plants with large seeds, such as Ludwigia, can still show high potential for long-distance dispersal. More attention should be paid to the role of waterbirds as vectors of alien plants and to the role of migratory geese as vectors of plants in general.Peer Reviewe

TABADO: "Evaluation of a smoking cessation program among Adolescents in Vocational Training Centers": Study protocol

<p>Abstract</p> <p>Background</p> <p>Most of the efforts to reduce teenagers' tobacco addiction have focused on smoking prevention and little on smoking cessation. A smoking cessation program (TABADO study), associating pharmacologic and cognitive-behavioural strategy, on a particularly vulnerable population (vocational trainees), was developed. This study aims to evaluate the efficacy of the program which was offered to all smokers in a population aged 15 to 20 years in Vocational Training Centers (VTC). This paper presents the TABADO study protocol.</p> <p>Methods</p> <p>The study is quasi-experimental, prospective, evaluative and comparative and takes place during the 2 years of vocational training. The final population will be composed of 2000 trainees entering a VTC in Lorraine, France, during the 2008-2009 period. The intervention group (1000 trainees) benefited from the TABADO program while no specific intervention took place in the "control" group (1000 trainees) other than the treatment and education services usually available. Our primary outcome will be the tobacco abstinence rate at 12 months.</p> <p>Discussion</p> <p>If the program proves effective, it will be a new tool in the action against smoking in populations that have been seldom targeted until now. In addition, the approach could be expanded to other young subjects from socially disadvantaged backgrounds in the context of a public health policy against smoking among adolescents.</p> <p>Trial registration</p> <p>Clinical trial identification number is NTC00973570.</p

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mix- ture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI=4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS

Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

OBJECTIVE: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RESULTS: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results

Water quality and planktonic microbial assemblages of isolated wetlands in an agricultural landscape

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Wetlands 31 (2011): 885-894, doi:10.1007/s13157-011-0203-6.Wetlands provide ecosystem services including flood protection, water quality enhancement, food chain support, carbon sequestration, and support regional biodiversity. Wetlands occur in human-altered landscapes, and the ongoing ability of these wetlands to provide ecosystem services is lacking. Additionally, the apparent lack of connection of some wetlands, termed geographically isolated, to permanent waters has resulted in little regulatory recognition. We examined the influence of intensive agriculture on water quality and planktonic microbial assemblages of intermittently inundated wetlands. We sampled 10 reference and 10 agriculturally altered wetlands in the Gulf Coastal Plain of Georgia. Water quality measures included pH, alkalinity, dissolved organic carbon, nutrients (nitrate, ammonium, and phosphate), and filterable solids (dry mass and ash-free dry mass). We measured abundance and relative size distribution of the planktonic microbial assemblage (< 45 μm) using flow cytometry. Water quality in agricultural wetlands was characterized by elevated nutrients, pH, and suspended solids. Autotrophic microbial cells were largely absent from both wetland types. Heterotrophic microbial abundance was influenced by nutrients and suspended matter concentration. Agriculture caused changes in microbial assemblages forming the base of wetland food webs. Yet, these wetlands potentially support important ecological services in a highly altered landscape.Funding was provided by the Joseph W. Jones Ecological Research Center.2012-07-2

Modeling denitrification in aquatic sediments

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 93 (2009): 159-178, doi:10.1007/s10533-008-9270-z.Sediment denitrification is a major pathway of fixed nitrogen loss from aquatic systems. Due to technical difficulties in measuring this process and its spatial and temporal variability, estimates of local, regional and global denitrification have to rely on a combination of measurements and models. Here we review approaches to describing denitrification in aquatic sediments, ranging from mechanistic diagenetic models to empirical parameterizations of nitrogen fluxes across the sediment-water interface. We also present a compilation of denitrification measurements and ancillary data for different aquatic systems, ranging from freshwater to marine. Based on this data compilation we reevaluate published parameterizations of denitrification. We recommend that future models of denitrification use (1) a combination of mechanistic diagenetic models and measurements where bottom waters are temporally hypoxic or anoxic, and (2) the much simpler correlations between denitrification and sediment oxygen consumption for oxic bottom waters. For our data set, inclusion of bottom water oxygen and nitrate concentrations in a multivariate regression did not improve the statistical fit.Financial support for AEG to work on the manuscript came from NSF NSF-DEB-0423565. KF, DB and DDT acknowledge support from NOAA CHRP grant NA07NOS4780191

Kappa free light chains is a valid tool in the diagnostics of MS : A large multicenter study

To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS