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Stress granules (SGs), formed by untranslated messenger ribonucleoproteins (mRNPs) during cellular stress in eukaryotes, have been linked to flavivirus interference without clear understanding. This study reveals the role of Zika virus (ZIKV) NS2B as a scaffold protein mediating interaction between protein phosphatase 1α (PP1α) and eukaryotic initiation factor 2α (eIF2α). This interaction promotes eIF2α dephosphorylation by PP1α, inhibiting SG formation. The NS2B-PP1α complex exhibits remarkable stability, resisting ubiquitin-induced degradation and amplifying eIF2α dephosphorylation, thus promoting ZIKV replication. In contrast, the NS2BV35A mutant, interacting exclusively with eIF2α, fails to inhibit SG formation, resulting in reduced viral replication and diminished impact on brain organoid growth. These findings reveal PP1α's dual role in ZIKV infection, inducing interferon production as an antiviral factor and suppressing SG formation as a viral promoter. Moreover, we found that NS2B also serves as a versatile mechanism employed by flaviviruses to counter host antiviral defenses, primarily by broadly inhibiting SG formation. This research advances our comprehension of the complex interplay in flavivirus-host interactions, offering potential for innovative therapeutic strategies against flavivirus infections. Author summary: Zika virus (ZIKV) belongs to vector-borne flaviviruses, associated with Guillain-Barré syndrome and neonatal microcephaly. Stress granules (SGs) which forms under stress in eukaryotic cells can interfere with viral replication. Although previous studies have indicated that ZIKV can interfere with SG formation, the precise molecular mechanism and function remain unclear. Exploration of the mechanisms by which ZIKV antagonizes SG formation may help to identify new antiviral approaches. Here, we found that ZIKV NS2B bridge PP1α and eIF2α to promote eIF2α dephosphorylation and SG inhibition. Meanwhile, Reciprocal inhibition of K48-linked ubiquitination stabilized NS2B and PP1α to further facilitate the dephosphorylation of eIF2α and the concurrent inhibition of SG formation. Conversely, we demonstrated that a mutant form of NS2B, NS2BV35A, which interacted solely with eIF2α and not PP1α, attenuated virus replication and mitigated neurotoxicity in brain organoid development. The NS2B-PP1α-eIF2α axis reveals a novel biological function of NS2B as a general mechanism for flavivirus evasion of host antiviral effects, providing new therapeutic strategies for antiviral study. [ABSTRACT FROM AUTHOR]

This study adopted hyperspectral imaging technology combined with machine learning to detect the disease severity of stem blight through the canopy of asparagus mother stem. Several regions of interest were selected from each hyperspectral image, and the reflection spectra of the regions of interest were extracted. There were 503 sets of hyperspectral data in the training set and 167 sets of hyperspectral data in the test set. The data were preprocessed using various methods and the dimension was reduced using PCA. K−nearest neighbours (KNN), decision tree (DT), BP neural network (BPNN), and extreme learning machine (ELM) were used to establish a classification model of asparagus stem blight. The optimal model depended on the preprocessing methods used. When modeling was based on the ELM method, the disease grade discrimination effect of the FD−MSC−ELM model was the best with an accuracy (ACC) of 1.000, a precision (PREC) of 1.000, a recall (REC) of 1.000, an F1-score (F1S) of 1.000, and a norm of the absolute error (NAE) of 0.000, respectively; when the modeling was based on the BPNN method, the discrimination effect of the FD−SNV−BPNN model was the best with an ACC of 0.976, a PREC of 0.975, a REC of 0.978, a F1S of 0.976, and a mean square error (MSE) of 0.072, respectively. The results showed that hyperspectral imaging of the asparagus mother stem canopy combined with machine learning methods could be used to grade and detect stem blight in asparagus mother stems. [ABSTRACT FROM AUTHOR]

We previously found that, among human parainfluenza virus type 3 (HPIV3) proteins, the interaction of nucleoprotein (N) and phosphoprotein (P) provides the minimal requirement for the formation of cytoplasmic inclusion bodies (IBs), which are sites of RNA synthesis, and that acetylated α-tubulin enhances IB fusion and viral replication. In this study, using immunoprecipitation and mass spectrometry assays, we determined that vimentin (VIM) specifically interacted with the N–P complex of HPIV3, and that the head domain of VIM was responsible for this interaction, contributing to the inhibition of IB fusion and viral replication. Furthermore, we found that VIM promoted the degradation of α-tubulin acetyltransferase 1 (α-TAT1), through its head region, thereby inhibiting the acetylation of α-tubulin, IB fusion, and viral replication. In addition, we identified a 20-amino-acid peptide derived from the head region of VIM that participated in the interaction with the N–P complex and inhibited viral replication. Our findings suggest that VIM inhibits the formation of HPIV3 IBs by downregulating α-tubulin acetylation via enhancing the degradation of α-TAT1. Our work sheds light on a new mechanism by which VIM suppresses HPIV3 replication. Author summary: Human parainfluenza virus type 3 (HPIV3) is one of the most common pathogenic respiratory RNA viruses, and its replication sites, known as inclusion bodies (IBs), which are formed by nucleoprotein (N) and phosphoprotein (P), are critical in viral RNA synthesis. Exploration of the mechanisms by which viral inclusion bodies are formed in cells may help to identify new antiviral approaches. Our aim was to identify cellular proteins with regulatory effects on the formation of viral IBs. The formation of HPIV3 IBs relies on acetylated α-tubulin, and we found that VIM negatively regulated α-tubulin acetylation by enhancing the degradation of α-TAT1, thereby suppressing the fusion and maturation of viral IBs. Based on the interaction between IBs and VIM, the peptide derived from amino-acid residues 61 to 80 in the VIM head region exerted antiviral effects, providing a new direction for our antiviral study. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is a powerful technique that enables fingerprinting of materials, molecules, and chemical environments by probing vibrational resonances. In many applications, the desired Raman signals are masked by fluorescence, either from the molecular system being studied, or from adjacent metallic nanostructures. Here, it is shown that wavelength‐modulated Raman spectroscopy provides a powerful way to significantly reduce the strength of the fluorescence background, thereby allowing the desired Raman signals to be clearly recorded. This approach is made use of to explore Raman scattering in the context of vibrational strong coupling, an area that has thus far been problematic to visualise. Specifically, strong coupling between the vibrational modes in a polymer and two types of confined light field, the fundamental mode of a metal‐clad microcavity, and the surface‐plasmon modes of an adjacent thin metal film are looked at. While clear advantages in using the wavelength‐modulated Raman approach are found, these results on strong coupling are inconclusive, and highlight the need for more work in this exciting topic area. [ABSTRACT FROM AUTHOR]

Task scheduling is important in cloud manufacturing because of customers' increasingly individualized demands. However, when various changes occur, a previous optimal schedule may become non-optimal or even infeasible owing to the uncertainty of the real manufacturing environment where dynamic task arrival over time is a vital source. In this paper, we propose a novel collaborative task scheduling (CTS) model dealing with new task arrival which considers multi-supply chain collaboration. We present an improved multi-population biogeography-based optimization (IMPBBO) algorithm that uses a matrix-based solution representation and integrates the multi-population strategy, local search for the best solution, and the collaboration mechanism, for determining the optimal schedule. A series of experiments are conducted for verifying the effectiveness of the IMPBBO algorithm for solving the CTS model by comparing it with five other algorithms. The experimental results concerning average best values obtained by the IMPBBO algorithm are better than that obtained by comparison algorithms for 41 out of 45 cases, showing its superior performance. Wilcoxon-test has been employed to strengthen the fact that IMPBBO algorithm performs better than five comparison algorithms. [ABSTRACT FROM AUTHOR]

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress. Author summary: Ebola virus (EBOV) is one of the deadliest pathogens, causing fatal hemorrhagic fever diseases in humans and primates. In this study, we find that P300-mediated NEDD4 acetylation facilitates EBOV egress. Acetylation promotes NEDD4-VP40 interactions which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. This study implies that inhibitory effect of acetylation can be regarded as an attractive candidate of drug target for the treatment of Ebola virus disease. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that changes in oxygenated hemoglobin concentration (O2Hb) in the prefrontal cortex (PFC) are associated with changes in cognitive function. Therefore, the present study aimed to explore the effect of differences in O2Hb levels in the left and right PFC (L-PFC and R-PFC, respectively) on cognitive function after exercise. This study included 12 healthy male college students. The exercise regimen consisted of 4 min of warm-up and rest each, followed by 20 min of moderate-intensity exercise and 20 min of post-exercise rest. Participants underwent the 2-back cognitive test thrice (pre-exercise, post-exercise, and after the 20 min post-exercise rest period), and their reaction times were recorded. O2Hb levels in the PFC were monitored using functional near-infrared spectroscopy. We analyzed the correlations between changes in post-exercise reaction times and differences in peak O2Hb levels (L-PFC minus R-PFC), area under the curve for O2Hb changes, and increases in the O2Hb slope during exercise. Peak O2Hb, area under the curve (AUC) for O2Hb change, and increase in the slope of O2Hb were significantly correlated with changes in reaction time. These findings provide insight into the mechanism by which O2Hb differences between the L-PFC and R-PFC affect cognitive function. [ABSTRACT FROM AUTHOR]

Glucosamine (GlcN), a dietary supplement widely utilized to promote joint health and effective in the treatment of osteoarthritis, is an effective macroautophagy/autophagy activator in vitro and in vivo. Previous studies have shown that autophagy is required for hepatitis B virus (HBV) replication and envelopment. The objective of this study was to determine whether and how GlcN affects HBV replication, using in vitro and in vivo experiments. Our data demonstrated that HBsAg production and HBV replication were significantly increased by GlcN treatment. Confocal microscopy and western blot analysis showed that the amount of autophagosomes and the levels of autophagic markers MAP1LC3/LC3-II and SQSTM1 were clearly elevated by GlcN treatment. GlcN strongly blocked autophagic degradation of HBV virions and proteins by inhibiting lysosomal acidification through its amino group. Moreover, GlcN further promoted HBV replication by inducing autophagosome formation via feedback inhibition of mechanistic target of rapamycin kinase complex 1 (MTORC1) signaling in an RRAGA (Ras related GTP binding A) GTPase-dependent manner. In vivo, GlcN application promoted HBV replication and blocked autophagic degradation in an HBV hydrodynamic injection mouse model. In addition, GlcN promoted influenza A virus, enterovirus 71, and vesicular stomatitis virus replication in vitro. In conclusion, GlcN efficiently promotes virus replication by inducing autophagic stress through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling. Thus, there is a potential risk of enhanced viral replication by oral GlcN intake in chronically virally infected patients. Abbreviations: ACTB: actin beta; ATG: autophagy-related; CMIA: chemiluminescence immunoassay; ConA: concanavalin A; CQ: chloroquine; CTSD: cathepsin D; DAPI: 4ʹ,6-diamidino-2-phenylindole; EV71: enterovirus 71; GalN: galactosamine; GFP: green fluorescence protein; GlcN: glucosamine; GNPNAT1: glucosamine-phosphate N-acetyltransferase 1; HBP: hexosamine biosynthesis pathway; HBV: hepatitis B virus; HBcAg: hepatitis B core antigen; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B e antigen; HBV RI: hepatitis B replicative intermediate; IAV: influenza A virus; LAMP1: lysosomal associated membrane protein 1; LAMTOR: late endosomal/lysosomal adaptor, MAPK and MTOR activator; ManN: mannosamine; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; PHH: primary human hepatocyte; RAB7: RAB7A, member RAS oncogene family; RPS6KB1: ribosomal protein S6 kinase B1; RRAGA: Ras related GTP binding A; RT-PCR: reverse transcriptase polymerase chain reaction; SEM: standard error of the mean; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; UAP1: UDP-N-acetylglucosamine pyrophosphorylase 1; VSV: vesicular stomatitis virus. [ABSTRACT FROM AUTHOR]

The effect of Bi2O3‐B2O3‐SiO2‐ZnO glass (denoted as BBSZ) content on the densification, microstructure, and electrical properties of ZnO‐based multilayer varistors (MLVs) has been investigated. In ZnO‐based (MLVs), BBSZ acted as a promoter in ZnO grain growth, which increased the grain size of ZnO, resulting in a decrease in breakdown voltage. Results showed that the adding of BBSZ glass had an improvement in densification and overall properties of MLVs. It was found that a maximum value of 5.45 g/cm3 of the bulk density and the optimum properties (V1mA = 27.28 V, α = 40.33, IL = 0.75 μA, Ip = 35 A) of ZnO‐based MLVs were achieved with 3 wt% BBSZ glass sintered at 925°C for 3 hours. [ABSTRACT FROM AUTHOR]

Horizontal cooperation in logistics refers to several logistics service providers cooperating to accomplish common goals, which usually involves a collaborative vehicle routing problem. In this paper, we present a new collaborative vehicle routing problem with rough location (CVRPRL), which considers both the security of sharing detailed customer information and the configuration of shared resource. We utilize the rough location of the customer to replace the detailed customer location and introduce the concept of collaborative logistics sharing degree in the CVRPRL model. Subsequently, the cost allocation mechanism is designed based on an extended Shapley value, which allocates fixed costs and risks in different ways. Further, an extended ant colony optimization (EACO) algorithm is proposed to solve the CVRPRL. The EACO algorithm combines both large neighborhood search and local search strategies. Finally, we perform a series of simulation experiments to verify the effectiveness of EACO compared with other meta-heuristic algorithms. [ABSTRACT FROM AUTHOR]

Viral infection causes many physiological alterations in the host cell, and many of these alterations can affect the host mitochondrial network, including mitophagy induction. A substantial amount of literature has been generated that advances our understanding of the relationship between mitophagy and several viruses. Some viruses trigger mitophagy directly, and indirectly and control the mitophagic process via different strategies. This enables viruses to promote persistent infection and attenuate the innate immune responses. In this review, we discuss the events of virus-regulated mitophagy and the functional relevance of mitophagy in the pathogenesis of viral infection and disease. Abbreviation: ATG: autophagy related; BCL2L13: BCL2 like 13; BNIP3L/NIX: BCL2 interacting protein 3 like; CL: cardiolipin; CSFV: classical swine fever virus; CVB: coxsackievirus B; DENV: dengue virus; DNM1L: dynamin 1 like; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; HPIV3: human parainfluenza virus 3; HSV-1: herpes simplex virus type 1; IMM: inner mitochondrial membrane; IAV: influenza A virus; IFN: interferon; IKBKE/IKKε: inhibitor of nuclear factor kappa B kinase subunit epsilon; LUBAC: linear ubiquitin assembly complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MAVS: mitochondrial antiviral signaling protein; MFF: mitochondria fission factor; NLRP3: NLR family pyrin domain containing 3; NDV: Newcastle disease virus; NR4A1: nuclear receptor subfamily 4 group A member 1; OMM: outer mitochondrial membrane; OPA1: OPA1, mitochondrial dynamin like GTPase; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; PHB2: prohibitin 2; PRRSV: porcine reproductive and respiratory syndrome virus; PRRs: pattern-recognition receptors; RLRs: RIG-I-like receptors; ROS: reactive oxygen species; RIPK2: receptor interacting serine/threonine kinase 2; SESN2: sestrin 2; SNAP29: synaptosome associated protein 29; STX17: syntaxin 17; TGEV: transmissible gastroenteritis virus; TUFM: Tu translation elongation factor, mitochondrial; TRAF2: TNF receptor associated factor 2; TRIM6: tripartite motif containing 6; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; VZV: varicella-zoster virus [ABSTRACT FROM AUTHOR]

The ability to provide quantitative, objective and automated pathological analysis would provide enormous benefits for national cancer screening programmes, in terms of both resource reduction and improved patient wellbeing. The move towards molecular pathology through spectroscopic methods shows great promise, but has been restricted by spectral quality, acquisition times and lack of direct clinical application. In this paper, we present the application of wavelength modulated Raman spectroscopy for the automated label‐ and fluorescence‐free classification of fixed squamous epithelial cells in suspension, such as those produced during a cervical smear test. Direct comparison with standard Raman spectroscopy shows marked improvement of sensitivity and specificity when considering both human papillomavirus (sensitivity +12.0%, specificity +5.3%) and transformation status (sensitivity +10.3%, specificity +11.1%). Studies on the impact of intracellular sampling location and storage effects suggest that wavelength modulated Raman spectroscopy is sufficiently robust to be used in fixed cell classification, but requires further investigations of potential sources of molecular variation in order to improve current clinical tools. [ABSTRACT FROM AUTHOR]

Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway. Furthermore, we found that inclusion body (IB) formation by the interaction of the nucleoprotein (N) and phosphoprotein (P) of HPIV3 correlated with SG suppression. In addition, co-expression of P with NL478A (a point mutant of N, which is unable to form IBs with P) or with NΔN10 (lacking N-terminal 10 amino acids of N, which could form IBs with P but was unable to synthesize or shield viral RNAs) failed to inhibit SG formation, suggesting that inhibition of SG formation also correlates with the capacity of IBs to synthesize and shield viral RNAs. Therefore, we provide a model whereby viral IBs escape the antiviral effect of SGs by concealing their own newly synthesized viral RNAs and offer new insights into the emerging role of IBs in viral replication. [ABSTRACT FROM AUTHOR]

Human parainfluenza virus type 3 is one of the main causes of lower respiratory illness in newborns and infants. The role of the matrix protein (M) in viral budding is extensively studied, but the effect of M on viral replication remains to be determined. Using an HPIV3 minigenome assay, we found that M reduced HPIV3 mingenome-encoded reporter activity even though it had an unspecific effect on the expression of cellular genes. Furthermore, the inhibition effect of M on viral RNA synthesis was proven to be independent of its virus-like particles (VLPs)' release ability. A VLP's defective mutant (ML302A) decreased the expression of minigenome reporter as wild type M did. Using an immunofluorescence assay, we found that M weakened the formation of inclusion bodies (IBs), although it did not co-localize with the IBs. Moreover, using another mutant, ML305A , which is defective in M-nucleoprotein (N) interaction, we found that ML305A had no effect on reporter activity and IB formation as the wild type of M did. Taken together, we conclude that M reduces the replication of HPIV3 and IB formation by M-N interaction. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) contain stalled messenger ribonucleoprotein complexes and are related to the regulation of mRNA translation. Picornavirus infection can interfere with the formation of SGs. However, the detailed molecular mechanisms and functions of picornavirus-mediated regulation of SG formation are not clear. Here, we found that the 2A protease of a picornavirus, EV71, induced atypical stress granule (aSG), but not typical stress granule (tSG), formation via cleavage of eIF4GI. Furthermore, 2A was required and sufficient to inhibit tSGs induced by EV71 infection, sodium arsenite, or heat shock. Infection of 2A protease activity-inactivated recombinant EV71 (EV71-2AC110S) failed to induce aSG formation and only induced tSG formation, which is PKR and eIF2α phosphorylation-dependent. By using a Renilla luciferase mRNA reporter system and RNA fluorescence in situ hybridization assay, we found that EV71-induced aSGs were beneficial to viral translation through sequestering only cellular mRNAs, but not viral mRNAs. In addition, we found that the 2A protease of other picornaviruses such as poliovirus and coxsackievirus also induced aSG formation and blocked tSG formation. Taken together, our results demonstrate that, on one hand, EV71 infection induces tSG formation via the PKR-eIF2α pathway, and on the other hand, 2A, but not 3C, blocks tSG formation. Instead, 2A induces aSG formation by cleaving eIF4GI to sequester cellular mRNA but release viral mRNA, thereby facilitating viral translation. [ABSTRACT FROM AUTHOR]

A major challenge in biophotonics is multimodal imaging to obtain both morphological and molecular information at depth. We demonstrate a hybrid approach integrating optical coherence tomography (OCT) with wavelength modulated spatially offset Raman spectroscopy (WM‐SORS). With depth colocalization obtained from the OCT, we can penetrate 1.2‐mm deep into strong scattering media (lard) to acquire up to a 14‐fold enhancement of a Raman signal from a hidden target (polystyrene) with a spatial offset. Our approach is capable of detecting both Raman and OCT signals for pharmaceutical particles embedded in turbid media and revealing the white matter at depth within a 0.6‐mm thick brain tissue layer. This depth resolved label‐free multimodal approach is a powerful route to analyze complex biomedical samples. [ABSTRACT FROM AUTHOR]

ABSTRACT With the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) as a model drug, a series of poly(vinyl alcohol)-starch (PVA-ST) composite films for controlled drug release were prepared by a casting method. The morphology, structure, and release properties were systematically investigated. The results show that when the PVA-ST composite film containing 2,4-D (PSD) was immersed in water, the drug-release rate was high, whereas the introduction of sodium montmorillonite (Na-MMT) and an alginate ion-crosslinking structure to PSD significantly reduced the release rate and maintained the sustained release of the model drug for a longer period. A leaching experiment through the soil layer showed that the PSD drug-loaded film with Na-MMT and the alginate ion-crosslinking structure (PSDMA) possessed good release properties. The cumulative leached amount of the herbicide 2,4-D after eight irrigations was reduced to 57.6% from 100%. In addition, the PSDMA film showed favorable mechanical and thermal properties. This composite film is expected to have potential applications in the fields of agriculture, drug delivery, and more. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45051. [ABSTRACT FROM AUTHOR]

The spatial coherence of organic light-emitting diodes (OLEDs) is an important parameter that has gained little attention to date. Here, we present a method for making quantitative measurements of the spatial coherence of OLEDs using a Young's double-slit experiment. The usefulness of the method is demonstrated by making measurements on a range of OLEDs with different emitters (iridium and europium complexes) and architectures (bottom and top emitting) and the fringe visibility is further manipulated by gratings embedded in external diffractive optical elements. Based on the experiments and simulation of the results, we quantitatively determine the spatial coherence lengths of several OLEDs and find them to be a few micrometers. A 60% increase in the spatial coherence length was observed when using a narrow bandwidth emitter and a metal-coated grating. [ABSTRACT FROM AUTHOR]

Determining the identity of cells of the immune system usually involves destructive fixation and chemical staining, or labeling with fluorescently labeled antibodies recognising specific cell surface markers. Completely label-free identification would be a significant advantage in conditions where untouched cells are a priority. We demonstrate here the use of Wavelength Modulated Raman Spectroscopy, to achieve label-free identification of purified, unfixed and untouched populations of major immune cell subsets isolated from healthy human donors. Using this technique we have been able to distinguish between CD4+ T lymphocytes, CD8+ T lymphocytes and CD56+ Natural Killer cells at specificities of up to 96%. Additionally, we have been able to distinguish between CD303+ plasmacytoid and CD1c+ myeloid dendritic cell subsets, the key initiator and regulatory cells of many immune responses. This demonstrates the ability to identify unperturbed cells of the immune system, and opens novel opportunities to analyse immunological systems and to develop fully label-free diagnostic technologies. [ABSTRACT FROM AUTHOR]

Summary: Autophagy is a multistep process in which cytoplasmic components, including invading pathogens, are captured by autophagosomes that subsequently fuse with degradative lysosomes. Negative-strand RNA viruses, including paramyxoviruses, have been shown to alter autophagy, but the molecular mechanisms remain largely unknown. We demonstrate that human parainfluenza virus type 3 (HPIV3) induces incomplete autophagy by blocking autophagosome-lysosome fusion, resulting in increased virus production. The viral phosphoprotein (P) is necessary and sufficient to inhibition autophagosome degradation. P binds to SNAP29 and inhibits its interaction with syntaxin17, thereby preventing these two host SNARE proteins from mediating autophagosome-lysome fusion. Incomplete autophagy and resultant autophagosome accumulation increase extracellular viral production but do not affect viral protein synthesis. These findings highlight how viruses can block autophagosome degradation by disrupting the function of SNARE proteins. [Copyright &y& Elsevier]