Background Pseudorabies virus (PRV) is a common pathogen in multiple animal species particularly in pigs. However, PRV infection in humans is rare and to the best of knowledge, PRV has never been isolated from human cases before. Methods Four acute encephalitis cases in humans were confirmed as PRV infection based on clinical symptoms, laboratory diagnosis, and metagenomic next-generation sequencing (mNGS). Cerebrospinal fluid (CSF) samples were collected and applied for virus isolation. Etiological and genetic characteristics of this PRV human isolate were further determined. Results The patients manifested respiratory dysfunction and acute neurological symptoms. The mNGS revealed PRV specific nucleotide sequences in patients’ CSF samples (7-6198 reads and 0.2446%-80.58% coverage). The PRV envelope glycoprotein B antibody, glycoprotein E antibody, and neutralizing antibody were positively detected. For the first time, a PRV strain, designated hSD-1/2019, was isolated and identified from one CSF sample, and transmission electron microscopy revealed hSD-1/2019 had typical morphology similar to swine PRV. Phylogenetic analysis illustrated that hSD-1/2019 was genetically closest to those PRV variant strains currently circulating in pigs in China, and this strain showed similar etiological characteristics to Chinese PRV variant strains, while different from Chinese classical strain. Moreover, hSD-1/2019 showed high pathogenicity and induced acute neurological symptoms in pigs. Conclusions A PRV strain was isolated from an acute human encephalitis case. This isolate showed close phylogenetic relationships and similar etiological characteristics to Chinese PRV variant strains, implying the great risk of PRV transmission from pigs to humans.

Yu et al. demonstrate that the transcription factor Bcl11b is specifically expressed in mouse innate lymphoid progenitors committed to the ILC2 lineage and is required for their development. Bcl11b-deficient mice exhibit a complete lack of ILC2 development, which is confirmed by immune challenges with either papain treatment or influenza virus infection.

BackgroundHematopoietic stem cells (HSCs) are a rare cell type with the ability of long-term self-renewal and multipotency to reconstitute all blood lineages. HSCs are typically purified from the bone marrow using cell surface markers. Recent studies have identified significant cellular heterogeneities in the HSC compartment with subsets of HSCs displaying lineage bias. We previously discovered that the transcription factor Bcl11a has critical functions in the lymphoid development of the HSC compartment.ResultsIn this report, we employ single-cell transcriptomic analysis to dissect the molecular heterogeneities in HSCs. We profile the transcriptomes of 180 highly purified HSCs (Bcl11a+/+ and Bcl11a−/−). Detailed analysis of the RNA-seq data identifies cell cycle activity as the major source of transcriptomic variation in the HSC compartment, which allows reconstruction of HSC cell cycle progression in silico. Single-cell RNA-seq profiling of Bcl11a−/− HSCs reveals abnormal proliferative phenotypes. Analysis of lineage gene expression suggests that the Bcl11a−/− HSCs are constituted of two distinct myeloerythroid-restricted subpopulations. Remarkably, similar myeloid-restricted cells could also be detected in the wild-type HSC compartment, suggesting selective elimination of lymphoid-competent HSCs after Bcl11a deletion. These defects are experimentally validated in serial transplantation experiments where Bcl11a−/− HSCs are myeloerythroid-restricted and defective in self-renewal.ConclusionsOur study demonstrates the power of single-cell transcriptomics in dissecting cellular process and lineage heterogeneities in stem cell compartments, and further reveals the molecular and cellular defects in the Bcl11a-deficient HSC compartment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0739-5) contains supplementary material, which is available to authorized users.

SUMMARYAtFes1A is induced by high temperatures, and encodes a protein containing the armadillo repeat motif. Little is known about its biological function, however. In this study, we observed an increased heat-sensitive phenotype in atfes1a mutants, suggesting the involvement of AtFes1A in acquired thermotolerance. We found that AtFes1A is cytosolic and associates with cytosolic Hsp70. Loss of AtFes1A leads to a selective reduction of cytosolic Hsp70 and a global increase in heat shock transcription. Thus, AtFes1A appears to prevent cytosolic Hsp70 degradation, and acts as a negative regulator of heat-shock transcription. We also found increased ubiquitination of total protein in atfes1a mutants after severe heat stress. These findings suggest that AtFes1A plays an important role in heat response signalling pathways, in addition to its role in thermotolerance.

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Despite the ubiquity of organophosphate flame retardants (OPFRs) metabolites in the biota, the endocrine disrupting potency has not been well examined. Herein, we chose three primary metabolites of OPFRs (BCIPP, BDCIPP, and DPHP) to investigate their potential endocrine disrupting effects by in vitro, in vivo, and in silico assays. Three metabolites were agonistic to rat estrogenic receptor alpha (ERα) and antagonists to human mineralocorticoid receptor (MR). BCIPP exerted endocrine disrupting effect contrasting to the negative response of its parental compound. It also poses the strongest binding capacity to ERα among the tested compounds. Both BCIPP and BDCIPP upregulated the genes encoded for estrogenic synthesis enzymes in H295R cells, including 17βHSD and CYP19. All three compounds stimulated the transcription of CYP11B1, whereas BCIPP and DPHP also triggered CYP11B2, encoding for corticoid production. BDCIPP inhibits genes for progesterone synthesis including CYP11A1, STAR, and 3-βHSD. The induction of mortality and low hatchability of zebrafish embryo were ranked as BCIPP ≥ BDCIPP > DPHP. All compounds lead to malformation of zebrafish larvae. Both of the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary−gonadal axes were disrupted, with the highest impact by BCIPP. Altogether, the data clarified OPFRs metabolites may produce comparable or even higher endocrine disrupting effects than OPFRs.

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Organophosphorus flame retardants (OPFRs), a replacement for brominated flame retardants, have gradually been accepted as endocrine disrupting chemicals (EDCs). Recently, evidence has shown that these EDCs could cause chronic health problems, such as obesity, and referred to as metabolic disruptors. However, the disturbance to lipid metabolism caused by OPFRs remains poorly understood, especially at biological molecular levels. Herein, we used the human hepatocellular cells (HepG2) to study the lipid metabolism disruption caused by nine OPFRs (halogenated-, aryl-, and alkyl-containing). All the tested OPFRs, excluding the long carbon chain alkyl-OPFRs, could cause intracellular triglyceride (TG) and/or total cholesterol (TC) accumulation. In detail, aryl-OPFRs (TPhP and TCP) induced both TC and TG deposition. Halogenated-OPFRs (TCEP, TBPP, TDCPP, and TCPP) induced intracellular TG accumulation, and only TDCPP also induced TC accumulation. Furthermore, TPhP induced lipid accumulation through regulation genes encoding proteins involved in fatty acid β-oxidation, lipid, and fatty acid synthesis. All the halogenated-OPFRs cause TG accumulation only, enacted through β-oxidation rather than lipid synthesis. TPhP and TDCPP induced TC accumulation through both PPARγ and srebp2 signaling. Mitochondrial dysfunction including decreased oxygen consumption rate and ATP content may also contribute to lipid metabolic disruption by the tested OPFRs. Our data indicated that halogenated- and aryl-OPFRs may not be safe candidates, and further information should be made available as potential for, as well as the mechanism of, metabolic disruption. And long carbon chain alkyl-OPFRs may be safer than the other two groups.