Bur Buttercup, Ranunculus testiculatus, New to Eastern Canada

Bur Buttercup (Ranunculus testiculatus) is newly reported for eastern Canada based on two collections from campgrounds in southern Ontario. This vernal, annual, Eurasian weed is widespread in western North America and is expanding its range in the east; it should be expected elsewhere in eastern Canada. Bur Buttercup is known to be toxic to livestock

Using transcranial magnetic stimulation to investigate the acute effects of translingual neurostimulation in individuals with Multiple Sclerosis

Introduction: Non-invasive neuromodulation techniques have emerged as a promising treatment to facilitate rehabilitation for individuals with Multiple Sclerosis (MS). One neuromodulation method, translingual neurostimulation (TLNS), involves electrical stimulation of the tongue and when paired with physiotherapy, is proposed to improve gait and balance in individuals with MS. Studies reporting the efficacy of TLNS for improving gait and balance in several neurological disorders are not congruent and the actual mechanisms underlying TLNS is not fully understood. Non-invasive brain stimulation devices such as transcranial magnetic stimulation (TMS) can help elucidate how TLNS may work to influence plasticity and recovery. Methods: Participants were recruited from a clinical trial in which individuals with multiple sclerosis (MS) were randomized to receive either a real or modified TLNS device. TMS variables, including resting motor threshold (RMT), active motor threshold (AMT) and recruitment curves (excitatory and inhibitory) were measured pre and post a 20-minute TLNS stimulation. Results: A repeated measures ANOVA using mixed models was conducted to investigate changes in corticospinal excitability between the TLNS stimulation and sham groups pre and post stimulation. Comparing pre and post RMT, AMT and REC values, there were no significant differences in maximum stimulator output (%MSO), motor evoked potential (MEP) amplitude latency or cortical silent period (CSP) between the stimulation and sham groups (p > 0.1). Conclusion: Our analysis of the TMS variables, RMT, AMT and recruitment curves, indicate that 20 minutes of TLNS did not increase corticospinal excitability or decrease inhibition in individuals with MS. Future research will interrogate overall brain activation through changes in cerebral blood flow

Antiviral activity of the EB peptide against zoonotic poxviruses

<p>Abstract</p> <p>Background</p> <p>The EB peptide is a 20-mer that was previously shown to have broad spectrum <it>in vitro </it>activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for <it>in vitro </it>activity against the zoonotic orthopoxviruses cowpox and monkeypox and for <it>in vivo </it>activity in mice against vaccinia and cowpox.</p> <p>Findings</p> <p>In yield reduction assays, EB had an EC₅₀of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC₅₀for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox <it>in vitro </it>by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited <it>in vitro </it>by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no <it>in vivo </it>activity against cowpox in mice.</p> <p>Conclusions</p> <p>While EB did demonstrate some <it>in vivo </it>efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment <it>in vitro </it>than as a therapeutic against orthopoxviruses <it>in vivo</it>.</p

Magnetospheric considerations for solar system ice state

The current lattice configuration of the water ice on the surfaces of the inner satellites of Jupiter and Saturn is likely shaped by many factors. But laboratory experiments have found that energetic proton irradiation can cause a transition in the structure of pure water ice from crystalline to amorphous. It is not known to what extent this process is competitive with other processes in solar system contexts. For example, surface regions that are rich in water ice may be too warm for this effect to be important, even if the energetic proton bombardment rate is very high. In this paper, we make predictions, based on particle flux levels and other considerations, about where in the magnetospheres of Jupiter and Saturn the ∼MeV proton irradiation mechanism should be most relevant. Our results support the conclusions of Hansen and McCord (2004), who related relative level of radiation on the three outer Galilean satellites to the amorphous ice content within the top 1 mm of surface. We argue here that if magnetospheric effects are considered more carefully, the correlation is even more compelling. Crystalline ice is by far the dominant ice state detected on the inner Saturnian satellites and, as we show here, the flux of bombarding energetic protons onto these bodies is much smaller than at the inner Jovian satellites. Therefore, the ice on the Saturnian satellites also corroborates the correlation

Studies of a Lacustrine-Volcanic Mars Analog Field Site with Mars-2020-like Instruments

On the upcoming Mars‐2020 rover two remote sensing instruments, Mastcam‐Z and SuperCam, and two microscopic proximity science instruments, SHERLOC and PIXL, will collect compositional (mineralogy, chemistry, and organics) data essential for paleoenvironmental reconstruction. The synergies between and limitations of these instruments were evaluated via study of a Mars analog field site in the Mojave Desert, using instruments approximating the data that will be returned by Mars‐2020. A ground truth dataset was generated for comparison to validate the results. The site consists of a succession of clay‐rich mudstones of lacustrine origin, interbedded tuffs, a carbonate‐silica travertine deposit, and gypsiferous mudstone strata. The major geological units were mapped successfully using simulated Mars‐2020 data. Simulated Mastcam‐Z data identified unit boundaries and Fe‐bearing weathering products. Simulated SuperCam passive shortwave infrared and green Raman data were essential in identifying major mineralogical composition and changes in lacustrine facies at distance; this was possible even with spectrally downsampled passive IR data. LIBS and simulated PIXL data discriminated and mapped major element chemistry. Simulated PIXL revealed mm‐scale zones enriched in zirconium, of interest for age dating. SHERLOC‐like data mapped sulfate and carbonate at sub‐mm scale; silicates were identified with increased laser pulses/spot or by averaging of hundreds of spectra. Fluorescence scans detected and mapped varied classes of organics in all samples, characterized further with follow‐on spatially targeted deep‐UV Raman spectra. Development of dedicated organics spectral libraries is needed to aid interpretation. Given these observations, the important units in the outcrop would be sampled and cached for sample return

Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2

BACKGROUND: A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic was characterized by mild illness and belongs to the American genotype of DEN-2 viruses. To prepare a vaccine candidate, a previously described 30 nucleotide deletion (Δ30) in the 3' untranslated region of DEN-4 has been engineered into the DEN-2 isolate. METHODS: A full-length cDNA clone was generated from the DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2Δ30. Viruses were evaluated for replication in SCID mice transplanted with human hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys. Neutralizing antibody induction and protective efficacy were also assessed in rhesus monkeys. RESULTS: The rDEN2Δ30 virus was ten-fold reduced in replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2 viruses were not infectious for Aedes mosquitoes, but both readily infected Toxorynchites mosquitoes. In rhesus monkeys, rDEN2Δ30 appeared to be slightly attenuated when compared to the parent virus as measured by duration and peak of viremia and neutralizing antibody induction. A derivative of rDEN2Δ30, designated rDEN2Δ30-4995, was generated by incorporation of a point mutation previously identified in the NS3 gene of DEN-4 and was found to be more attenuated than rDEN2Δ30 in SCID-HuH-7 mice. CONCLUSIONS: The rDEN2Δ30 and rDEN2Δ30-4995 viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine

A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained responses by lapatinib in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, ependymoma, and high-grade glioma (HGG) undergoing resection were stratified and randomized to pre-resection treatment with lapatinib 900 mg/m(2) dose bid for 7-14 days or no treatment. Western blot analysis of ERBB expression and pathway activity in fresh tumor obtained at surgery estimated ERBB receptor signaling inhibition in vivo. Drug concentration was simultaneously assessed in tumor and plasma. In the phase II study, patients, stratified by histology, received lapatinib continuously, to assess sustained response. Eight patients, on the MB trial (four medulloblastomas, four ependymomas), received a median of two courses (range 1-6+). No intratumoral target inhibition by lapatinib was noted in any patient. Tumor-to-plasma ratios of lapatinib were 10-20 %. In the 34 patients (14 MB, 10 HGG, 10 ependymoma) in the phase II study, lapatinib was well-tolerated at 900 mg/m(2) dose bid. The median number of courses in the phase II trial was two (range 1-12). Seven patients (three medulloblastoma, four ependymoma) remained on therapy for at least four courses range (4-26). Lapatinib was well-tolerated in children with recurrent or CNS malignancies, but did not inhibit target in tumor and had little single agent activity.Fil: Fouladi, Maryam. St. Jude Children’s Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children’s Research Hospital; Estados UnidosFil: Blaney, Susan M.. Baylor College of Medicine. Texas Children’s Cancer Center; Estados UnidosFil: Onar Thomas, Arzu. St. Jude Children’s Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. St. Jude Children’s Research Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Packer, Roger J.. Children’s National Medical Center; Estados UnidosFil: Goldman, Stewart. Anne and Robert H. Lurie Children’s Hospital of Chicago; Estados UnidosFil: Geyer, J. Rusell. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Gajjar, Amar. St. Jude Children’s Research Hospital; Estados UnidosFil: Kun, Larry E.. St. Jude Children’s Research Hospital; Estados UnidosFil: Boyett, James M.. St. Jude Children’s Research Hospital; Estados UnidosFil: Gilbertson, Richard J.. St. Jude Children’s Research Hospital; Estados Unido

A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

AbstractAn acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Δ30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host

Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Δ30 with those of DEN1

BACKGROUND: Antigenic chimeric viruses have previously been generated in which the structural genes of recombinant dengue virus type 4 (rDEN4) have been replaced with those derived from DEN2 or DEN3. Two vaccine candidates were identified, rDEN2/4Δ30(ME) and rDEN3/4Δ30(ME), which contain the membrane (M) precursor and envelope (E) genes of DEN2 and DEN3, respectively, and a 30 nucleotide deletion (Δ30) in the 3' untranslated region of the DEN4 backbone. Based on the promising preclinical phenotypes of these viruses and the safety and immunogenicity of rDEN2/4Δ30(ME) in humans, we now describe the generation of a panel of four antigenic chimeric DEN4 viruses using either the capsid (C), M, and E (CME) or ME structural genes of DEN1 Puerto Rico/94 strain. RESULTS: Four antigenic chimeric viruses were generated and found to replicate efficiently in Vero cells: rDEN1/4(CME), rDEN1/4Δ30(CME), rDEN1/4(ME), and rDEN1/4Δ30(ME). With the exception of rDEN1/4(ME), each chimeric virus was significantly attenuated in a SCID-HuH-7 mouse xenograft model with a 25-fold or greater reduction in replication compared to wild type DEN1. In rhesus monkeys, only chimeric viruses with the Δ30 mutation appeared to be attenuated as measured by duration and magnitude of viremia. rDEN1/4Δ30(CME) appeared over-attenuated since it failed to induce detectable neutralizing antibody and did not confer protection from wild type DEN1 challenge. In contrast, rDEN1/4Δ30(ME) induced 66% seroconversion and protection from DEN1 challenge. Presence of the Δ30 mutation conferred a significant restriction in mosquito infectivity upon rDEN1/4Δ30(ME) which was shown to be non-infectious for Aedes aegypti fed an infectious bloodmeal. CONCLUSION: The attenuation phenotype in SCID-HuH-7 mice, rhesus monkeys, and mosquitoes and the protective immunity observed in rhesus monkeys suggest that rDEN1/4Δ30(ME) should be considered for evaluation in a clinical trial