Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

In vitro evaluation of chloroquine-loaded and heparin surface-functionalized solid lipid nanoparticles

Abstract Background Use of chloroquine, an otherwise safe and relatively affordable anti-malarial drug, was discontinued due to widespread prevalence of resistant parasites. Many entrant anti-malarial drugs for treatment of chloroquine resistant malaria raises the concerns of cost and safety among other challenges. Innovative ways of circumventing chloroquine resistance is of paramount importance. Such may include nanoparticulate delivery strategies and targeting. This study evaluated physicochemical properties and in vitro antiplasmodial activity of chloroquine encapsulated heparin functionalized solid lipid nanoparticles (CQ-Hep-SLNs) and non-heparin functionalized SLNs (CQ-SLN) against Plasmodium falciparum. Methods The modified double-emulsion solvent evaporation technique was used to prepare the nanoparticles. HPLC/UV was used to determine the in vitro drug release. The semi-automated micro-dilution technique was adapted in assessing the in vitro antiplasmodial activity to give drug concentration capable of inhibiting 50% of the P. falciparum (IC50), as a function of antiplasmodial efficacy. Results Prepared nanoparticles were below 500 nm in size with % drug loading (%DL) between 21 and 25% and encapsulation efficiency (%EE) of 78–90%. The drug-loaded SLN exhibited a biphasic drug release profile at pH 7.4, with an initial burst release during the first 24 h followed by sustained release in both formulations. Nanoformulated CQ-SLN (4.72 ± 0.14 ng/mL) and CQ-Hep-SLN (2.41 ± 0.27 ng/mL), showed enhanced in vitro antiplasmodial activities against chloroquine sensitive (D6) strain of P. falciparum, albeit with no activity against the chloroquine resistant W2 strain, compared to free CQ standard (5.81 ± 0.18 ng/mL). Conclusions These findings suggest that the nanoformulated drugs displayed enhanced anti-malarial activities against chloroquine sensitive (D6) strains of P. falciparum compared to the free CQ standard. There is some form of potential dual synergistic effect of CQ-loaded heparinized solid lipid nanoparticles (Hep-SLN), meaning that combining heparin and CQ in SLNs has beneficial effects, including potential for specific targeting of parasitized red blood cells as afforded by heparin. Thus, the study has produced SLNs nanoparticles that have superior in vitro activities than CQ on CQ-sensitive parasites

The effects of a DNA virus infection on the reproductive potential of female tsetse flies, Glossina morsitans centralis and Glossina morsitans morsitans (Diptera: Glossinidae)

Reproductive anomalies associated with the tsetse DNA virus infection in the female tsetse hosts, Glossina morsitans centralis Machado and Glossina morsitans morsitans Westwood, inoculated with the virus during the 3rd instar larval stage were studied and the data compared to those obtained from the control females injected with sterile physiological saline. Virus infected flies had significantly longer first and second pregnancy cycles (P<0.0001) and produced pupae that were of significantly less weight in milligrams (P<0.0001) compared to controls. Transmission of the virus to progeny was not absolute and only 21% of G. m. centralis and 48% of G. m. morsitans first progeny flies from infected females developed salivary gland hypertrophy as a result of transmission from mother to progeny. The virus infected females produced significantly fewere pupae compared to the controls during the experimental period (P<0.00001)

Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable <i>P. falciparum</i> Infection

<div><p>Clinical immunity to malaria declines in the absence of repeated parasite exposure. However, little is known about how B cell populations and antigen-specific memory B cells change in the absence of <i>P. falciparum</i> infection. A successful indoor residual insecticide spraying campaign in a highland area of western Kenya, led to an absence of blood-stage <i>P. falciparum</i> infection between March 2007 and April 2008. We assessed memory B cell responses in 45 adults at the beginning (April 2008) and end (April 2009) of a subsequent 12-month period during which none of the adults had evidence of asymptomatic parasitemia or clinical disease. Antibodies and memory B cells to the 42-kDa portion of the merozoite surface protein-1 (MSP-1₄₂) were measured using ELISA and ELISPOT assays, respectively. B cell populations were characterized by flow cytometry. From 2008 to 2009, the prevalence of MSP-1₄₂-specific memory B cells (45% vs. 55%, respectively, <i>P</i> = 0.32) or antibodies (91% vs. 82%, respectively, <i>P</i> = 0.32) did not differ significantly, although specific individuals did change from positive to negative and vice versa, particularly for memory B cells, suggesting possible low-level undetected parasitemia may have occurred in some individuals. The magnitude of MSP-1₄₂-specific memory B cells and levels of antibodies to MSP-1₄₂ also did not differ from 2008 to 2009 (<i>P</i>>0.10 for both). However, from 2008 to 2009 the proportions of both class-switched atypical (CD19+IgD-CD27-CD21-IgM-) and class-switched activated (CD19+IgD-CD27+CD21-IgM-) memory B cells decreased (both <i>P</i><0.001). In contrast, class-switched resting classical memory B cells (CD19+IgD-CD27+CD21+IgM-) increased (<i>P</i><0.001). In this area of seasonal malaria transmission, a one- year absence of detectable <i>P. falciparum</i> infection was not associated with changes in the prevalence or level of MSP-1₄₂ specific memory B cells, but was associated with major changes in overall memory B cell subsets.</p></div

The gating strategy for identifying the B cell subpopulations.

<p>We first gated on the live (DAPI⁻) lymphocytes and then collected 10,000 events of CD19+. These were analyzed for expression of IgD, CD27, CD21, IgM and FcRL4. CD19+ lymphocytes were classified as naïve (IgD+CD27-) B cells, non class-switched (IgD+CD27+) MBCs, classical (IgD-CD27+) MBCs and double negative (IgD-CD27-) MBCs. MBC subtypes were further defined as follows: 1. Resting classical MBCs: CD19+IgD-CD27+CD21+. 2. Activated MBCs: CD19+IgD-CD27+CD21-. 3. Atypical MBCs: CD19+IgD-CD27-CD21- MBCs.</p

Number and percentages of responders to tetanus toxoid (TT) as assessed by specific memory B cells and immunoglobulin G (IgG) antibodies (Ab) in April 2009.

<p>McNemar’s test, <i>P = </i>0.71.</p

Prevalence of Immunoglobulin G (IgG) antibodies to the merozoite-surface protein-1 (42) (MSP-1₄₂) in highland Kenyan adults in 2008 and 2009.

<p>McNemar’s test, <i>P</i> = 0.32.</p

The distribution of FcRL4+ memory B cell subsets.

<p>The percentage of FcRL4+ CD19+IgD-CD27-CD21 MBCs had a non-significant increase (A) but the mean fluorescence intensity (MFI) of FcRL4+ cells increased significantly (B). Lines in 7A reflect mean values and comparison is with t-test. Lines in 7B reflect median values and comparison is with Wilcox on signed rank test because MFI values were not normally distributed.</p