Open-source genomic analysis of Shiga-toxin–producing E. coli O104:H4

An outbreak caused by Shiga-toxin–producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the family. This analysis involved the use of rapid, bench-top DNA sequencing technology, open-source data release, and prompt crowd-sourced analyses. In less than a week, these studies revealed that the outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance

Evaluating the effectiveness of three national marine protected areas in the Yangtze River Delta, China

China’s coastal areas face serious environmental degradation as a consequence of large-scale economic development. To balance environmental sustainability with economic development, China is currently implementing a strategy of ‘eco-civilization’, with marine protected areas (MPAs) expected to be one approach to achieving sustainable marine ecosystems. Since the 1990s, China has established over 270 MPAs, but their effectiveness remains unknown, particularly in the Yangtze River Delta. This study modified pre-existing frameworks to evaluate the effectiveness of three national MPAs in the Yangtze River Delta. The modified framework includes conservation outcomes and their potential drivers. Drivers consist of – attributes species or ecosystems within the MPA, attributes of the MPA, institutional design principles, and participation. Five scenarios were proposed based on score combinations of the four drivers: proactive, well designed, well governed, interactive, and learning. All three MPAs achieved a satisfactory level of outcomes and most of the drivers for all three MPAs achieved a satisfactory level. Two of the MPAs were categorized into the learning scenario, and the third into the well-designed scenario, indicating that there is still room to improve institutional design principles and public participation. We suggest developing cost and benefit indicators to more deeply understand proportionality among stakeholders. In addition, the role of participation should be clarified and promoted. We recommend regular environmental performance monitoring and assessment to identify problems and optimize management

Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice

IntroductionIncreased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function and underlying mechanisms of NETs in TBI-induced neuronal cell death are not yet fully understood.MethodsFirst, brain tissue and peripheral blood samples of TBI patients were collected, and NETs infiltration in TBI patients was detected by immunofluorescence staining and Western blot. Then, a controlled cortical impact device was used to model brain trauma in mice, and Anti-Ly6G, DNase, and CL-amidine were given to reduce the formation of neutrophilic or NETs in TBI mice to evaluate neuronal death and neurological function. Finally, the pathway changes of neuronal pyroptosis induced by NETs after TBI were investigated by administration of peptidylarginine deiminase 4 (a key enzyme of NET formation) adenovirus and inositol-requiring enzyme-1 alpha (IRE1α) inhibitors in TBI mice.ResultsWe detected that both peripheral circulating biomarkers of NETs and local NETs infiltration in the brain tissue were significantly increased and had positive correlations with worse intracranial pressure (ICP) and neurological dysfunction in TBI patients. Furthermore, the depletion of neutrophils effectively reduced the formation of NET in mice subjected to TBI. we found that degradation of NETs or inhibition of NET formation significantly inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 1 (NLRP1) inflammasome-mediated neuronal pyroptosis after TBI, whereas these inhibitory effects were abolished by cyclic GMP-AMP (cGAMP), an activator of stimulating Interferon genes (STING). Moreover, overexpression of PAD4 in the cortex by adenoviruses could aggravate NLRP1-mediated neuronal pyroptosis and neurological deficits after TBI, whereas these pro-pyroptotic effects were rescued in mice also receiving STING antagonists. Finally, IRE1α activation was significantly upregulated after TBI, and NET formation or STING activation was found to promote this process. Notably, IRE1α inhibitor administration significantly abrogated NETs-induced NLRP1 inflammasome-mediated neuronal pyroptosis in TBI mice.DiscussionOur findings indicated that NETs could contribute to TBI-induced neurological deficits and neuronal death by promoting NLRP1-mediated neuronal pyroptosis. Suppression of the STING/ IRE1α signaling pathway can ameliorate NETs-induced neuronal pyroptotic death after TBI

Label-free immunoassay for porcine circovirus type 2 based on excessively tilted fiber grating modified with staphylococcal protein A

Using excessively tilted fiber grating (Ex-TFG) inscribed in standard single mode fiber, we developed a novel label-free immunoassay for specific detection of porcine circovirus type 2 (PCV2), which is a minim animal virus. Staphylococcal protein A (SPA) was used to modify the silanized fiber surface thus forming a SPA layer, which would greatly enhance the proportion of anti-PCV2 monoclonal antibody (MAb) bioactivity, thus improving the effectiveness of specific adsorption and binding events between anti-PCV2 MAbs and PCV2 antigens. Immunoassay experiments were carried out by monitoring the resonance wavelength shift of the proposed sensor under different PCV2 titer levels. Anti-PCV2 MAbs were thoroughly dissociated from the SPA layer by treatment with urea, and recombined to the SPA layer on the sensor surface for repeated immunoassay of PCV2. The specificity of the immunosensor was inspected by detecting porcine reproductive and respiratory syndrome virus (PRRSV) first, and PCV2 subsequently. The results showed a limit of detection (LOD) for the PCV2 immunosensor of ~9.371TCID50/mL, for a saturation value of ~4.801×103TCID50/mL, with good repeatability and excellent specificity

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

CRL4 antagonizes SCFFbxo7-mediated turnover of cereblon and BK channel to regulate learning and memory

Intellectual disability (ID), one of the most common human developmental disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4) and can target voltage- and calcium-activated BK channel for ER retention. Here we report that ID-associated CRL4CRBNmutations abolish the interaction of the BK channel with CRL4, and redirect the BK channel to the SCFFbxo7ubiquitin ligase for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record density-dependent decrease of BK currents, which can be restored by blocking Cullin ubiquitin ligase activity. Importantly, mice with neuron-specific deletion of DDB1 or CRBN express reduced BK protein levels in the brain, and exhibit similar impairment in learning and memory, a deficit that can be partially rescued by activating the BK channel. Our results reveal a competitive targeting of the BK channel by two ubiquitin ligases to achieve exquisite control of its stability, and support changes in neuronal excitability as a common pathogenic mechanism underlying CRL4CRBN–associated ID

Mass testing of the JUNO experiment 20-inch PMTs readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a multi-purpose, large size, liquid scintillator experiment under construction in China. JUNO will perform leading measurements detecting neutrinos from different sources (reactor, terrestrial and astrophysical neutrinos) covering a wide energy range (from 200 keV to several GeV). This paper focuses on the design and development of a test protocol for the 20-inch PMT underwater readout electronics, performed in parallel to the mass production line. In a time period of about ten months, a total number of 6950 electronic boards were tested with an acceptance yield of 99.1%