Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

Visceral leishmaniasis (VL), a vector-transmitted disease caused by Leishmania donovani, is potentially fatal if left untreated. Vaccination against VL has received limited attention compared with cutaneous leishmaniasis, although the need for an effective vaccine is pressing for the control of the disease. Earlier, we observed protective efficacy using leishmanial antigen (Ag) in the presence of either cationic liposomes or monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) against experimental VL through the intraperitoneal (i.p.) route of administration in the mouse model. However, this route of immunization is not adequate for human use. For this work, we developed vaccine formulations combining cationic liposomes with MPL-TDM using recombinant GP63 (rGP63) as protein Ag through the clinically relevant subcutaneous (s.c.) route. Two s.c. injections with rGP63 in association with cationic liposomes and MPL-TDM showed enhanced immune responses that further resulted in high protective levels against VL in the mouse model. This validates the combined use of MPL-TDM as an immunopotentiator and liposomes as a suitable vaccine delivery system

The Influence of Recent Climate Change on Tree Height Growth Differs with Species and Spatial Environment

Tree growth has been reported to increase in response to recent global climate change in controlled and semi-controlled experiments, but few studies have reported response of tree growth to increased temperature and atmospheric carbon dioxide (CO2) concentration in natural environments. This study addresses how recent global climate change has affected height growth of trembling aspen (Populus tremuloides Michx) and black spruce (Picea mariana Mill B.S.) in their natural environments. We sampled 145 stands dominated by aspen and 82 dominated by spruce over the entire range of their distributions in British Columbia, Canada. These stands were established naturally after fire between the 19th and 20th centuries. Height growth was quantified as total heights of sampled dominant and co-dominant trees at breast-height age of 50 years. We assessed the relationships between 50-year height growth and environmental factors at both spatial and temporal scales. We also tested whether the tree growth associated with global climate change differed with spatial environment (latitude, longitude and elevation). As expected, height growth of both species was positively related to temperature variables at the regional scale and with soil moisture and nutrient availability at the local scale. While height growth of trembling aspen was not significantly related to any of the temporal variables we examined, that of black spruce increased significantly with stand establishment date, the anomaly of the average maximum summer temperature between May-August, and atmospheric CO2 concentration, but not with the Palmer Drought Severity Index. Furthermore, the increase of spruce height growth associated with recent climate change was higher in the western than in eastern part of British Columbia. This study demonstrates that the response of height growth to recent climate change, i.e., increasing temperature and atmospheric CO2 concentration, did not only differ with tree species, but also their growing spatial environment

Functional Promoter Polymorphisms Govern Differential Expression of HMG-CoA Reductase Gene in Mouse Models of Essential Hypertension

3-Hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase gene (Hmgcr) is a susceptibility gene for essential hypertension. Sequencing of the Hmgcr locus in genetically hypertensive BPH (blood pressure high), genetically hypotensive BPL (blood pressure low) and genetically normotensive BPN (blood pressure normal) mice yielded a number of single nucleotide polymorphisms (SNPs). BPH/BPL/BPN Hmgcr promoter-luciferase reporter constructs were generated and transfected into liver HepG2, ovarian CHO, kidney HEK-293 and neuronal N2A cells for functional characterization of the promoter SNPs. The BPH-Hmgcr promoter showed significantly less activity than the BPL-Hmgcr promoter under basal as well as nicotine/cholesterol-treated conditions. This finding was consistent with lower endogenous Hmgcr expression in liver and lower plasma cholesterol in BPH mice. Transfection experiments using 5′-promoter deletion constructs (strategically made to assess the functional significance of each promoter SNP) and computational analysis predicted lower binding affinities of transcription factors c-Fos, n-Myc and Max with the BPH-promoter as compared to the BPL-promoter. Corroboratively, the BPH promoter-luciferase reporter construct co-transfected with expression plasmids of these transcription factors displayed less pronounced augmentation of luciferase activity than the BPL construct, particularly at lower amounts of transcription factor plasmids. Electrophoretic mobility shift assays also showed diminished interactions of the BPH promoter with HepG2 nuclear proteins. Taken together, this study provides mechanistic basis for the differential Hmgcr expression in these mouse models of human essential hypertension and have implications for better understanding the role of this gene in regulation of blood pressure

The Role of Gamma-Band Activity in the Representation of Faces: Reduced Activity in the Fusiform Face Area in Congenital Prosopagnosia

Congenital prosopagnosia (CP) describes an impairment in face processing that is presumably present from birth. The neuronal correlates of this dysfunction are still under debate. In the current paper, we investigate high-frequent oscillatory activity in response to faces in persons with CP. Such neuronal activity is thought to reflect higher-level representations for faces.Source localization of induced Gamma-Band Responses (iGBR) measured by magnetoencephalography (MEG) was used to establish the origin of oscillatory activity in response to famous and unknown faces which were presented in upright and inverted orientation. Persons suffering from congenital prosopagnosia (CP) were compared to matched controls.Corroborating earlier research, both groups revealed amplified iGBR in response to upright compared to inverted faces predominately in a time interval between 170 and 330 ms and in a frequency range from 50-100 Hz. Oscillatory activity upon known faces was smaller in comparison to unknown faces, suggesting a "sharpening" effect reflecting more efficient processing for familiar stimuli. These effects were seen in a wide cortical network encompassing temporal and parietal areas involved in the disambiguation of homogenous stimuli such as faces, and in the retrieval of semantic information. Importantly, participants suffering from CP displayed a strongly reduced iGBR in the left fusiform area compared to control participants.In sum, these data stress the crucial role of oscillatory activity for face representation and demonstrate the involvement of a distributed occipito-temporo-parietal network in generating iGBR. This study also provides the first evidence that persons suffering from an agnosia actually display reduced gamma band activity. Finally, the results argue strongly against the view that oscillatory activity is a mere epiphenomenon brought fourth by rapid eye-movements (micro saccades)

A Full Suite of Histone and Histone Modifying Genes Are Transcribed in the Dinoflagellate Lingulodinium

BACKGROUND: Dinoflagellates typically lack histones and nucleosomes are not observed in DNA spreads. However, recent studies have shown the presence of core histone mRNA sequences scattered among different dinoflagellate species. To date, the presence of all components required for manufacturing and modifying nucleosomes in a single dinoflagellate species has not been confirmed. METHODOLOGY AND RESULTS: Analysis of a Lingulodinium transcriptome obtained by Illumina sequencing of mRNA shows several different copies of each of the four core histones as well as a suite of histone modifying enzymes and histone chaperone proteins. Phylogenetic analysis shows one of each Lingulodinium histone copies belongs to the dinoflagellate clade while the second is more divergent and does not share a common ancestor. All histone mRNAs are in low abundance (roughly 25 times lower than higher plants) and transcript levels do not vary over the cell cycle. We also tested Lingulodinium extracts for histone proteins using immunoblotting and LC-MS/MS, but were unable to confirm histone expression at the protein level. CONCLUSION: We show that all core histone sequences are present in the Lingulodinium transcriptome. The conservation of these sequences, even though histone protein accumulation remains below currently detectable levels, strongly suggests dinoflagellates possess histones

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta