Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
sing a sample of ($10.09$ ± $0.04$) × 109 J/ψ events collected with the BESIII detector operating at the BEPCII storage ring, a partial wave analysis of the decay J/ψ → γηη' is performed. The first ...observation of an isoscalar state with exotic quantum numbers JPC = 1-+, denoted as η1(1855), is reported in the process J/ψ → γη1(1855) with η1(1855) → ηη'. Its mass and width are measured to be ($1855$ ± $9^{+6}_{-1}$) MeV/c2 and ( $188$ ± $18^{+3}_{-8}$) MeV, respectively, where the first uncertainties are statistical and the second are systematic, and its statistical significance is estimated to be larger than 19σ.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Based on a sample of ( 10.09±0.04 ) ×109 J/ψ events collected with the BESIII detector operating at the BEPCII storage ring, a partial wave analysis of the decay J/ψ → γηη' is performed. An isoscalar ...state with exotic quantum numbers JPC=1-+ , denoted as η1 ( 1855 ) , has been observed for the first time with statistical significance larger than 19σ . Its mass and width are measured to be ( 1855±9-1+6 ) MeV/c2 and ( 188±18-8+3 ) MeV , respectively. The first uncertainties are statistical and the second are systematic. The product branching fraction B ( J/ψ → γη1 ( 1855 ) ) B ( η1 ( 1855 ) → ηη' ) is measured to be ( 2.70±0.41-0.35+0.16 ) ×10-6 . In addition, an upper limit on the ratio of branching fractions B ( f0 ( 1710 ) → ηη' ) / B ( f0 ( 1710 ) → ππ ) is determined to be 1.61×10-3 at 90% confidence level, which lends support to the hypothesis that the f0 ( 1710 ) has a large glueball component.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by ...specialized flippases. MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials. However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information. Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations. Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
The enumeration and characterization of circulating tumor cells (CTCs), found in the peripheral blood of cancer patients, provide a potentially accessible source for cancer diagnosis and prognosis. ...This work reports on a novel spiral microfluidic device with a trapezoidal cross-section for ultra-fast, label-free enrichment of CTCs from clinically relevant blood volumes. The technique utilizes the inherent Dean vortex flows present in curvilinear microchannels under continuous flow, along with inertial lift forces which focus larger CTCs against the inner wall. Using a trapezoidal cross-section as opposed to a traditional rectangular cross-section, the position of the Dean vortex core can be altered to achieve separation. Smaller hematologic components are trapped in the Dean vortices skewed towards the outer channel walls and eventually removed at the outer outlet, while the larger CTCs equilibrate near the inner channel wall and are collected from the inner outlet. By using a single spiral microchannel with one inlet and two outlets, we have successfully isolated and recovered more than 80% of the tested cancer cell line cells (MCF-7, T24 and MDA-MB-231) spiked in 7.5 mL of blood within 8 min with extremely high purity (400-680 WBCs mL(-1); ~4 log depletion of WBCs). Putative CTCs were detected and isolated from 100% of the patient samples (n = 10) with advanced stage metastatic breast and lung cancer using standard biomarkers (CK, CD45 and DAPI) with the frequencies ranging from 3-125 CTCs mL(-1). We expect this simple and elegant approach can surmount the shortcomings of traditional affinity-based CTC isolation techniques as well as enable fundamental studies on CTCs to guide treatment and enhance patient care.
Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the ...esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members.
Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that ...patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.
We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.
We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.
The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A
bstract
Using
e
+
e
−
collision data corresponding to a total integrated luminosity of 12.9 fb
−
1
collected with the BESIII detector at the BEPCII collider, the exclusive Born cross sections and ...the effective form factors of the reaction
e
+
e
−
→
Ξ
−
Ξ
¯
+
are measured via the single baryon-tag method at 23 center-of-mass energies between 3.510 and 4.843 GeV. Evidence for the decay
ψ
3770
→
Ξ
−
Ξ
¯
+
is observed with a significance of 4.5
σ
by analyzing the measured cross sections together with earlier BESIII results. For the other charmonium(-like) states
ψ
(4040),
ψ
(4160),
Y
(4230),
Y
(4360),
ψ
(4415), and
Y
(4660), no significant signal of their decay to
Ξ
−
Ξ
¯
+
is found. For these states, upper limits of the products of the branching fraction and the electronic partial width at the 90% confidence level are provided.