Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses.

A controllable vacuum-diffusion method for gradual phosphidation of carbon coated metallic Co nanoparticles into Co/CoP Janus nanoparticles is reported. Janus Co/CoP nanoparticles, as typical Mott-Schottky electrocatalysts, exhibit excellent hydrogen evolution reaction and oxygen evolution reaction performance in various electrolytes across wide pH range along with high durability. The Mott-Schottky Co/CoP catalyst can work as bifunctional electrode materials for overall water splitting in wide pH range and can achieve a current density of 10 mA cm −2 in neutral electrolyte at only 1.51 V.

Heterogeneous catalysts of inexpensive and reusable transition-metal are attractive alternatives to homogeneous catalysts; the relatively low activity of transition-metal nanoparticles has become the main hurdle for their practical applications. Here, the de novo design of a Mott–Schottky-type heterogeneous catalyst is reported to boost the activity of a transition-metal nanocatalyst through electron transfer at the metal/nitrogen-doped carbon interface. The Mott–Schottky catalyst of nitrogen-rich carbon-coated cobalt nanoparticles (Co@NC) was prepared through direct polycondensation of simple organic molecules and inorganic metal salts in the presence of g-C3N4 powder. The Co@NC with controllable nitrogen content and thus tunable Fermi energy and catalytic activity exhibited a high turnover frequency (TOF) value (8.12 mol methyl benzoate mol–1 Co h–1) for the direct, base-free, aerobic oxidation of benzyl alcohols to methyl benzoate; this TOF is 30-fold higher than those of the state-of-the-art transition-metal-based nanocatalysts reported in the literature. The presented efficient Mott–Schottky catalyst can trigger the synthesis of a series of alkyl esters and even diesters in high yields.

BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α-based therapies to IFN-α-free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia. METHODS.We conducted a clinical trial using the DAA sofosbuvir plus ribavirin (SOF/RBV) and performed detailed mRNA expression analysis in liver and peripheral blood from patients who achieved either a sustained virologic response (SVR) or relapsed. RESULTS.On-treatment viral clearance was accompanied by rapid downregulation of IFN-stimulated genes (ISGs) in liver and blood, regardless of treatment outcome. Analysis of paired pretreatment and end of treatment (EOT) liver biopsies from SVR patients showed that viral clearance was accompanied by decreased expression of type II and III IFNs, but unexpectedly increased expression of the type I IFN IFNA2. mRNA expression of ISGs was higher in EOT liver biopsies of patients who achieved SVR than in patients who later relapsed. CONCLUSION.These results suggest that restoration of type I intrahepatic IFN signaling by EOT may facilitate HCV eradication and prevention of relapse upon withdrawal of SOF/RBV. TRIAL REGISTRATION. ClinicalTrials.gov NCT01441180. FUNDING. Intramural Programs of the National Institute of Allergy and Infectious The Journal of Clinical Investigation C l i n i C a l M e d i C i n e3 3 5 3 jci.orgVolume 124 Number 8 August 2014We next evaluated on-treatment serum protein levels of select chemokines and cytokines and observed similar expression at baseline and during treatment comparing patients who achieved SVR versus those who relapsed (Supplemental Table 3). Serum levels of the IFN-inducible cytokine IP-10, the protein product of the CXCL10 gene that was downregulated in liver (Figure 2A), correlated significantly with baseline viral load ( Figure 3A). Expression decreased rapidly on-treatment, regardless of treatment outcome, and increased with relapse ( Figure 3B). Viral kinetic and IP-10 decline were significantly correlated ( Figure 3C and Table 1). IL-10 and IFN-γ decreased modestly during treatment, while expression of most other proteins did not change, including TGF-β1 and TIMP1, which are associated with hepatic fibrosis (Supplemental Table 3 and ref. 25).To assess whether a similar pattern of gene expression changes could be observed in the periphery, we performed microarray mRNA analysis in PBMCs collected before treatment, early in treatment (day 6-11), and at EOT (week 24) and identified a significant decrease of IFN signaling during treatment (Supplemental Figure 2 and Supplemental Table 4). qRT-PCR analysis in PBMCs confirmed rapid and sustained downregulation of I...

Aimed at developing a highly active and stable non-precious metal catalyst (NPMC) for oxygen reduction reaction (ORR) in acidic proton-exchange membrane fuel cells (PEMFCs), a novel NPMC was prepared by pyrolyzing a composite of carbon-supported Fe-doped graphitic carbon nitride (Fe−g-C 3 N 4 @C) above 700 °C. In this paper, the influence of the pyrolysis temperature and Fe content on ORR performance was investigated. Rotating disk electrode (RDE) and rotating ring-disk electrode (RRDE) studies reveal that, with a half-wave potential of 0.75 V [versus reversible hydrogen electrode (RHE)] and a H 2 O 2 yield of 2.6% at 0.4 V, the as-synthesized catalyst heat-treated at 750 °C with a Fe salt/dicyandiamide (DCD) mass ratio of 10% displays the optimal ORR activity and selectivity. Furthermore, the pyrolyzed Fe−N−C composite exhibits superior durability in comparison to that of commercial 20 wt % Pt/C in acidic medium, making it a good candidate for an ORR electrocatalyst in PEMFCs. KEYWORDS: non-precious metal catalyst (NPMC), oxygen reduction reaction (ORR), proton-exchange membrane fuel cell (PEMFC), carbon-supported Fe-doped g-C 3 N 4 (Fe−g-C 3 N 4 @C), pyrolysis, Fe−N−C composite