niryuu/sni-each-converted huggingface dataset:
Protein chips have emerged as a promising approach for a wide variety of applications including the identification of protein-protein interactions, protein-phospholipid interactions, small molecule targets, and substrates of proteins kinases. They can also be used for clinical diagnostics and monitoring disease states. This article reviews current methods in the generation and applications of protein microarrays. Understanding complex cellular systems will require the identification and analysis of each of its components and determining how they function together and are regulated. A critical step in this process is to determine the biochemical activities of the proteins and how these activities themselves are controlled and modified by other proteins. Traditionally, the biochemical activities of proteins have been elucidated by studying single molecules, one experiment at a time. This process is not optimal, as it is slow and labor intensive. In contrast to this traditional approach, high-throughput scientific methods have been developed in the last decade to optimize the study of large numbers of molecules, including DNA, proteins and metabolites. DNA microarrays in particular have proved valuable in genomic research (Schena et al., 1995) . They have been used to study gene expression patterns, to locate transcription factor binding sites, and to detect sequence mutations and deletions on a grand scale. However, DNA microarrays tell us only about the genes themselves and provide little information regarding the functions of the proteins they encode. More recently high throughput approaches have been developed for the study of proteins, including profiling of proteins using mass spectrometry (Gavin et al.,
Output: Protein Microarray Technology Types of protein microarrays
Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by chronic neuroinflammation, axonal damage, and demyelination. Cellular components of the adaptive immune response are viewed as important in initiating formation of demyelinating lesions in MS patients. This notion is supported by preclinical animal models, genome-wide association studies (GWAS), as well as approved disease modifying therapies (DMTs) that suppress clinical relapse and are designed to impede infiltration of activated lymphocytes into the CNS. Nonetheless, emerging evidence demonstrates that the innate immune response e.g., neutrophils can amplify white matter damage through a variety of different mechanisms. Indeed, using a model of coronavirus-induced neurologic disease, we have demonstrated that sustained neutrophil infiltration into the CNS of infected animals correlates with increased demyelination. This brief review highlights recent evidence arguing that targeting the innate immune response may offer new therapeutic avenues for treatment of demyelinating disease including MS.
Output: Clinical Medicine Innate Immune Responses and Viral-Induced Neurologic Disease
Remyelination is the phenomenon by which new myelin sheaths are generated around axons in the adult central nervous system (CNS). This follows the pathological loss of myelin in diseases like multiple sclerosis (MS). Remyelination can restore conduction properties to axons (thereby restoring neurological function) and is increasingly believed to exert a neuroprotective role on axons. Remyelination occurs in many MS lesions but becomes increasingly incomplete/inadequate and eventually fails in the majority of lesions and patients. EVorts to understand the causes for this failure of regeneration have fueled research into the biology of remyelination and the complex, interdependent cellular and molecular factors that regulate this process. Examination of the mechanisms of repair of experimental lesions has demonstrated that remyelination occurs in two major phases. The first consists of colonization of lesions by oligodendrocyte progenitor cells (OPCs), the second the diVerentiation of OPCs into myelinating oligodendrocytes that contact demyelinated INTERNATIONAL REVIEW OF 589 NEUROBIOLOGY, VOL. 79
Output: REMYELINATION IN MULTIPLE SCLEROSIS
Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus-host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.
Output: Virus-Host Coevolution with a Focus on Animal and Human DNA Viruses
Background: The replication of coronaviruses takes place on cytoplasmic double membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to be membrane anchors of the coronavirus replication complex. Nsp4 is localized to the ER membrane when expressed alone but is recruited into the replication complex in infected cells. It is revealed to contain four trans-membrane regions and its N-and C-termini are exposed to the cytosol. We have determined the crystal structures of the C-terminal hydrophilic domain of nsp4 (nsp4C) from MHV strain A59 and a C425S site-directed mutant. The highly conserved 89 amino acid region from T408 to Q496 is shown to possess a new fold. The wild-type (WT) structure features two monomers linked by a Cys425-Cys425 disulfide bond in one asymmetric unit. The monomers are arranged with their N-and C-termini in opposite orientations to form an ''open'' conformation. Mutation of Cys425 to Ser did not affect the monomer structure, although the mutant dimer adopts strikingly different conformations by crystal packing, with the cross-linked C-termini and parallel N-termini of two monomers forming a ''closed'' conformation. The WT nsp4C exists as a dimer in solution and can dissociate easily into monomers in a reducing environment. Conclusions/Significance: As nsp4C is exposed in the reducing cytosol, the monomer of nsp4C should be physiological. This structure may serve as a basis for further functional studies of nsp4.
Output: Crystal Structure of the C-Terminal Cytoplasmic Domain of Non-Structural Protein 4 from Mouse Hepatitis Virus A59
Objective: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. Methods: A total of 528 patients with viral pneumonia at RuiJin hospital in Shanghai from May 2015 to May 2019 were recruited. Multiplex real-time RT-PCR was used to detect respiratory viruses. Demographic information, comorbidities, routine laboratory examinations, immunological indexes, etiological detections, radiological images and treatment were collected on admission. Results: 76 (14.4%) patients died within 90 days in hospital. A predictive MuLBSTA score was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included multilobular infiltrates (OR = 5.20, 95% CI 1.41-12.52, p = 0.010; 5 points), lymphocyte ≤ 0.8 * 10 9 /L (OR = 4.53, 95% CI 2.55-8.05, p < 0.001; 4 points), bacterial coinfection (OR = 3.71, 95% CI 2.11-6.51, p < 0.001; 4 points), acute-smoker (OR = 3.19, 95% CI 1.34-6.26, p = 0.001; 3 points), quit-smoker (OR = 2.18, 95% CI 0.99-4.82, p = 0.054; 2 points), hypertension (OR = 2.39, 95% CI 1.55-4.26, p = 0.003; 2 points) and age ≥60 years (OR = 2.14, 95% CI 1.04-4.39, p = 0.038; 2 points). 12 points was used as a cut-off value for mortality risk stratification. This model showed sensitivity of 0.776, specificity of 0.778 and a better predictive ability than CURB-65 (AUROC = 0.773 vs. 0.717, p < 0.001). Conclusion: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. It can accurately stratify hospitalized patients with viral pneumonia into relevant risk categories and could provide guidance to make further clinical decisions.
Output: Citation: Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score
The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by nextgeneration sequencing (NGS) of associated RNA molecules. Two viruses with negative-and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3' untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection.
Output: Comparative analysis of viral RNA signatures on different RIG-I-like receptors
PRRSV PEDV Antiviral inhibitor Broad-spectrum 3C-like serine/3C-like protease A B S T R A C T Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are highly virulent and contagious porcine pathogens that cause tremendous economic losses to the swine industry worldwide. Currently, there is no effective treatment for PRRSV and PEDV, and commercial vaccines do not induce sterilizing immunity. In this study, we screened a library of 1000 compounds and identified two specific inhibitors, designated compounds 2 and 3, which target the PRRSV 3C-like serine protease (3CLSP). First, we evaluated the inhibitory effects of compounds 2 and 3 on PRRSV 3CLSP activity. Next, we determined the anti-PRRSV capacity of compounds 2 and 3 in MARC-145 cells and obtained EC 50 and CC 50 values of 57 μM (CC 50 = 479.9 μM) and 56.8 μM (CC 50 = 482.8 μM), respectively. Importantly, compounds 2 and 3 also targeted the PEDV 3C-like protease (3CL protease) and inhibited PEDV replication, showing EC 50 and CC 50 values of 100 μM (CC 50 = 533.8 μM) and 57.9 μM (CC 50 = 522.3 μM), respectively. Finally, our results indicated that the active sites (His39 in 3CLSP and His41 in 3CL protease) were conservative, and contacted compounds 2 and 3 via hydrogen bonds and hydrophobic forces in the putative substrate-binding models. In summary, compounds 2 and 3 exhibit broad-spectrum antiviral activity and may facilitate the development of antiviral drugs against PRRSV and PEDV.
Output: Identification of two antiviral inhibitors targeting 3C-like serine/3C-like protease of porcine reproductive and respiratory syndrome virus and porcine epidemic diarrhea virus A R T I C L E I N F O
Influenza A H7N9 virus has caused five outbreak waves of human infections in China since 2013 and posed a dual challenge to public health and poultry industry. There is an urgent need to develop an effective vaccine to reduce its pandemic potential. In the present study, we evaluated the biochemical characteristics and immunogenicity of two H7 virus-like particles (VLPs) composed of the matrix 1 (M1) and hemagglutinin of wild-type (HA-WT) or hemagglutinin of whose transmembrane domain replaced by that from H3N2 subtype (HA-TM). H7 VLPs-WT and H7 VLPs-TM could assemble and release into the supernatant of Sf9 cells and they had similar morphological characteristics. However, compared to H7 VLPs-WT, H7 VLPs-TM had more trimeric HA proteins and could better resist thermal changes. In mice H7 VLPs-TM induced higher titers of HI, IgG, IgG2a and IFN-c, and provided better protection against homologous and heterologous H7N9 viruses (no matter belonging to Yangtze River Delta or Pearl River Delta) challenge with less weight loss and higher survival rate. In summary, H7 VLPs-TM represents a potential strategy for the development of H7N9 vaccines.
Output: H7 virus-like particles assembled by hemagglutinin containing H3N2 transmembrane domain and M1 induce broad homologous and heterologous protection in mice
Pulmonary edema (PE) may occur with enterovirus 71 (EV71) infection. We monitored arterial pressure (AP) and heart rate (HR) in patients with EV71 infection and analyzed the variability of AP and HR. Sympathetic activity, AP, and HR increased with respiratory stress. Thereafter, parasympathetic activity increased with decreases in AP and HR. The lungs showed edema with inducible nitric oxide synthase (iNOS) expression. Destruction of the medial, ventral, and caudal medulla may lead to sympathetic overactivation, causing blood to shift to the lungs. The pathogenesis of PE may also involve iNOS and nitric oxide. Epidemic or sporadic infection with enterovirus 71 (EV71) usually occurs during the summer months. Children infected with EV71 develop rashes on the hand, foot, and mouth. Most patients recover without complications. Some patients manifest signs such as headache, profuse sweating, lethargy, paraparesis, and weakness of the limbs. Several patients infected with EV71 have died of fulminant pulmonary edema (PE) soon after infection [1, 2] . The pathogenesis of PE is still unknown. Chang et al. [2] postulated that viral destruction of the CNS may be the cause of death. Central sympathetic activation resulting in systemic vasoconstriction and the shift of blood volume to the pulmonary region of the circulatory system, as demonstrated in earlier findings from our laboratory, was used to explain centrogenic PE [2, 3] . However, studies by Chang et al. [1, 2] did not provide pathological evidence of CNS lesions, nor did they assess autonomic activity. In the present study, we report CNS lesions in patients associated with PE due to enterovirus
Output: Mechanism of Fulminant Pulmonary Edema Caused by Enterovirus 71
This chapter defi nes and describes early warning systems (EWS) by examining structures and functions of EWS. The focus of this book is on climate change, but other hazards help to better illustrate and understand EWS in the context of climate change. These include hazards which manifest rapidly, such as tsunamis, as well as creeping hazards which manifest slowly, such as drought. The fundamental tenet is that each EWS needs to be viewed as a social process which often involves technical components embedded in their social context. That leads to a preference for a 'First Mile' approach for designing EWS, which involves communities from the beginning of developing an EWS, rather than a 'Last Mile' approach, which adds people and communities towards the end of the design process. By keeping people and communities at the centre of an EWS from the beginning, the EWS can contribute to daily life and livelihoods, thereby supporting wider disaster risk reduction and sustainable development endeavours, rather than being a separate system waiting to be triggered only when a hazard appears. Yet any EWS has limitations. Those limitations need to be recognised and overcome through other approaches, with possibilities being to consider 'medium warning' and 'late warning' systems rather than just early warning.
Output: Early Warning Systems Defi ned
Many viruses can cause respiratory diseases in humans. Although great advances have been achieved in methods of diagnosis, it remains challenging to identify pathogens in unexplained pneumonia (UP) cases. In this study, we applied next-generation sequencing (NGS) technology and a metagenomic approach to detect and characterize respiratory viruses in UP cases from Guizhou Province, China. A total of 33 oropharyngeal swabs were obtained from hospitalized UP patients and subjected to NGS. An unbiased metagenomic analysis pipeline identified 13 virus species in 16 samples. Human rhinovirus C was the virus most frequently detected and was identified in seven samples. Human measles virus, adenovirus B 55 and coxsackievirus A10 were also identified. Metagenomic sequencing also provided virus genomic sequences, which enabled genotype characterization and phylogenetic analysis. For cases of multiple infection, metagenomic sequencing afforded information regarding the quantity of each virus in the sample, which could be used to evaluate each viruses' role in the disease. Our study highlights the potential of metagenomic sequencing for pathogen identification in UP cases. unexplained pneumonia, metagenomics, next-generation sequencing Citation: ). Simultaneous virus identification and characterization of severe unexplained pneumonia cases using a metagenomics sequencing technique. Sci China Life Sci 60, 279-286.
Output: SCIENCE CHINA Simultaneous virus identification and characterization of severe unexplained pneumonia cases using a metagenomics sequencing technique
Polysaccharides are natural biopolymers that have been recognized to be the most promising hosts for the synthesis of metallic nanoparticles (MNPs) because of their outstanding biocompatible and biodegradable properties. Polysaccharides are diverse in size and molecular chains, making them suitable for the reduction and stabilization of MNPs. Considerable research has been directed toward investigating polysaccharide-based metallic nanoparticles (PMNPs) through host-guest strategy. In this review, approaches of preparation, including top-down and bottom-up approaches, are presented and compared. Different characterization techniques such as scanning electron microscopy, transmission electron microscopy, dynamic light scattering, UV-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction and small-angle X-ray scattering are discussed in detail. Besides, the applications of PMNPs in the field of wound healing, targeted delivery, biosensing, catalysis and agents with antimicrobial, antiviral and anticancer capabilities are specifically highlighted. The controversial toxicological effects of PMNPs are also discussed. This review can provide significant insights into the utilization of polysaccharides as the hosts to synthesize MPNs and facilitate their further development in synthesis approaches, characterization techniques as well as potential applications.
Output: polymers Preparation, Characterization and Application of Polysaccharide-Based Metallic Nanoparticles: A Review
Advances in biological sciences have outpaced regulatory and legal frameworks for biosecurity. Simultaneously, there has been a convergence of scientific disciplines such as synthetic biology, data science, advanced computing and many other technologies, which all have applications in health. For example, advances in cybercrime methods have created ransomware attacks on hospitals, which can cripple health systems and threaten human life. New kinds of biological weapons which fall outside of traditional Cold War era thinking can be created synthetically using genetic code. These convergent trajectories are dramatically expanding the repertoire of methods which can be used for benefit or harm. We describe a new risk landscape for which there are few precedents, and where regulation and mitigation are a challenge. Rapidly evolving patterns of technology convergence and proliferation of dual-use risks expose inadequate societal preparedness. We outline examples in the areas of biological weapons, antimicrobial resistance, laboratory security and cybersecurity in health care. New challenges in health security such as precision harm in medicine can no longer be addressed within the isolated vertical silo of health, but require cross-disciplinary solutions from other fields. Nor can they cannot be managed effectively by individual countries. We outline the case for new cross-disciplinary approaches in risk analysis to an altered risk landscape. Keywords Biosecurity · Cybersecurity · Terrorism · Disasters · Health intelligence Advances in biological sciences have occurred at a faster rate than changes in regulatory and legal frameworks for biosecurity. An equally profound change is the convergence of concepts and methods from scientific disciplines that were previously distinct and siloed. Innovations in genomics, synthetic biology, big data, computing science and many other technologies have applications in health and medicine. Equally important, these convergent trajectories are dramatically expanding the repertoire of dual-use technologies-those which can be harnessed for benefit or harm to humanity. Collectively, these trends are shaping a new landscape for systematic risk analysis, for which there are
Output: Converging and emerging threats to health security
Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K + , Na + , Cl − , Ca 2+ ) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development.
Output: Scorpion Venom-Toxins that Aid in Drug Development: A Review
Background: As designated points of entry (PoEs) play a critical role in preventing the transmission of international public health risks, huge efforts have been invested in Taiwan to improve the core capacities specified in the International Health Regulations 2005 (IHR 2005). This article reviews how Taiwan strengthened the core capacities at the Taoyuan International Airport (TIA) and the Port of Kaohsiung (PoK) by applying a new, practicable model. Design: An IHR PoE program was initiated for implementing the IHR core capacities at designated PoEs. The main methods of this program were 1) identifying the designated PoEs according to the pre-determined criteria, 2) identifying the competent authority for each health measure, 3) building a close collaborative relationship between stakeholders from the central and PoE level, 4) designing three stages of systematic assessment using the assessment tool published by the World Health Organization (WHO), and 5) undertaking action plans targeting the gaps identified by the assessments. Results: Results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed a continuous progressive trend at the TIA (86, 91, and 100%, respectively), and at the PoK (77, 97, and 99.9%, respectively). The results of the follow-up external assessment indicated that both these designated PoEs already conformed to the IHR requirements. These achievements were highly associated with strong collaboration, continuous empowerment, efficient resource integration, and sustained commitments. Conclusions: Considering that many countries had requested for an extension on the deadline to fulfill the IHR 2005 core capacity requirements, Taiwan's experiences can be a source of learning for countries striving to fully implement these requirements. Further, in order to broaden the scope of public health protection into promoting global security, Taiwan will keep its commitments on multisectoral cooperation, human resource capacity building, and maintaining routine and emergency capacities.
Output: Building core capacities at the designated points of entry according to the International Health Regulations 2005: a review of the progress and prospects in Taiwan
Family cluster Human-to-human transmission Air transmission s u m m a r y Objectives: To identify human-to-human transmission of H7N9 avian influenza virus, we investigated a hospital cluster combined with family cluster in this study. Methods: We obtained and analyzed clinical, epidemiological and virological data from the three patients. RT-PCR, viral culture and sequencing were conducted for determination of causative pathogen. Results: The index case presented developed pneumonia with fever after exposure to chicken in a poultry farm. Case A presented pneumonia with high fever on day 3 after she shared a hospital room with the index case. Case B, the father of the index case, presented pneumonia with high fever on day 15 after he took care of the index case. H7N9 virus circulated in the local farm to which the index case was exposed. Full genomic sequence of virus showed 99.8-100% identity shared between the index case and case A or case B. Compared to the earliest virus of Anhui, a total of 29 amino acid variation sites were observed in the 8 segments. Conclusions: A hospital cluster combined with family cluster of H7N9 avian influenza infection was identified. Air transmission resulted in the hospital cluster possibly. A poultry farm was the initially infectious source of the cluster.
Output: A hospital cluster combined with a family cluster of avian influenza H7N9 infection in Anhui Province, China
Background: Since late December 2019, novel coronavirus-infected pneumonia (NCP) emerged in Wuhan, Hubei province, China. Meanwhile, NCP rapidly spread from China to other countries, and several countries' government rush to evacuate their citizens from Wuhan. We analyzed the infection rate of the evacuees and extrapolated the results in Wuhan's NCP incidence estimation. Methods: We collected the total number and confirmed cases of 2019-nCov infection in the evacuation of Korea, Japan, Germany, Singapore, and France and estimated the infection rate of the 2019 novel coronavirus (2019-nCov) among people who were evacuated from Wuhan with a meta-analysis. NCP incidence of Wuhan was indirectly estimated based on data of evacuation.
Output: Epidemic size of novel coronavirus-infected pneumonia in the Epicenter Wuhan: using data of five-countries' evacuation action
a b c d MERS-CoV NP Podocin Merge 50 µm Supplementary figure 1. Productive MERS-CoV replication in a primary human podocyte cell line. (a) Co-immunohistochemical staining of MERS-CoV NP (green) and a podocytespecific marker, podocin (red) in a primary human podocyte cell line 1 24 h after the challenge of MERS-CoV. (b) Western blot analysis of MERS-CoV NP in MERS-CoV-and mock-infected podocytes. γ-tubulin was also detected as a loading control. Total RNAs (c) and the conditioned media (d) of the MERS-CoV-inoculated podocytes were harvested for viral load detection at the indicated time-points using RT-qPCR as previously described. 2 The MERS-CoV RNA from the cell lysates were normalized to the expression level of GAPDH mRNA. Images shown in a and b are representatives of three independent experiments. Error bars shown in c and d represent the mean ± s.d. of three independent experiments. Statistical significance was evaluated by Student's t-tests and the ranges of p-values were indicated in c and d. Samples from a, b, c and d represent biological replicates. NATURE MICROBIOLOGY | www.nature.com/naturemicrobiology 1 2 50 µm 50 µm Supplementary figure 2. Apoptosis due to MERS-CoV infection in kidney cells or overexpression of Smad7 and FGF2 in uninfected kidney cells. (a) HK2 cells were infected by MERS-CoV or SARS-CoV at M.O.I. = 9.6, separately. At different time-points (0, 16, 28 and 34 hpi), the infected cells were assayed by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) assays. The degree of apoptosis (top) was measured by counting the number of positively stained cells (red focal stain; bottom) over the total number of cells in the counted fields (blue nuclei counterstained by DAPI; bottom). Statistical analyses of the percentage of apoptotic cells induced by MERS-CoV over that of SARS-CoV were evaluated by Student's ttests and the ranges of p-values were indicated on top of each time-point. Immunostainings of the virus NP (green; bottom) in each infection condition were included. (b) HK2 cells were transfected with overexpression constructs of Smad7 and FGF2 followed by the detection of apoptosis using TUNEL assays as described above. Different doses of cDNA (0, 0.25 and 0.5 μg) were first topped up to 0.5 μg with their vector backbone plasmids followed by transfection. The degree of apoptosis (top) was measured by counting the number of positively stained cells (red focal stain; bottom) over the total number of cells in the counted fields (blue nuclei counterstained by DAPI; bottom). Images shown in a and b are representatives of three independent experiments. Error bars shown in a and b represent the mean ± s.d. of three independent experiments. Statistical significance was evaluated by Student's t-tests and the ranges of p-values were indicated in a and b. Samples from a and b represent biological replicates. NATURE MICROBIOLOGY | www.nature.com/naturemicrobiology
Output: MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2
Background: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. Methods: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015-16 in Finland. Swabs from surface samples, and air samples were tested by realtime PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43).
Output: Deposition of respiratory virus pathogens on frequently touched surfaces at airports
Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.
Output: Vaccination against Paediatric Respiratory Pathogens
Mice expressing the Cre recombinase from within the lysozyme M locus (LysMcre mice) were purchased from the Jackson Laboratory (Strain # 004781). Atg5 flox/flox and Atg5 flox/flox +LysMcre mice with two different backgrounds ( Figures 1C and 1D from mixed 129-C57BL/6 mice and all the others from C57BL/6 mice) were used for this study and consistent phenotypes between different backgrounds were observed. To generate bone marrow derived macrophages (BMDM), mouse bone marrows were isolated and cultured on non-tissue-culture treated plate for 7 days in BMDM media (Dulbeco's Modified Eagle Medium, 10% fetal bovine serum, 5% horse serum, 10% CMG14-12 (Takeshita et al., 2000) , 1x MEM nonessential amino acids, 1mM sodium pyruvate, 2 mM L-glutamine). At day 7, adherent BMDMs were dissociated from the plate and set up for experiment. At day 10, media were changed to fresh media and IFNγ were treated if necessary. At day 11, cells were used for MNV infection or autophagy analysis. Depending on the deletion status of floxed gene (e.g. Atg7 flox/flox +LysMcre), BMDMs were cultured up to 21 days and used for infection study. For EMCV and MHV, BMDMs were prepared as previously described (Zhao et al., 2007) .
Output: Cell Host & Microbe Supplemental Information Nondegradative Role of Atg5-Atg12/ Atg16L1 Autophagy Protein Complex in Antiviral Activity of Interferon Gamma
Influenza viruses cause respiratory infections every epidemic season regardless of the patient's age. The aim of this study was to determine the activity of respiratory viruses in the epidemic season 2016/2017 in Poland, with particular emphasis on influenza viruses among people aged over 14. There were 2982 clinical samples taken from patients from four age groups: 15-25, 26-44, 45-64, and 65 years tested under the Sentinel and non-Sentinel surveillance programs. The presence of influenza viruses was confirmed in more than 40% of cases, the predominant type was influenza A virus unsubtyped, followed by subtype A/H3N2/. The results for the four age groups indicate that the highest number of confirmed respiratory viruses was recorded in individuals 65 years of age, slightly less, in the decreasing order, in the age groups 45-64 years, 15-25 years, and 26-44 years. Influenza type B infections were observed only in sporadic cases. Given the epidemiological data, epidemic season 2016/ 2017 was characterized by similar dynamics compared to the previous season in Poland and also in most of the European countries. More than 4 million cases and suspected cases of influenza and influenza-like viruses have been reported in Poland, more than 16,000 hospitalizations, and 25 deaths, of which 20 cases occurred among people 65 years of age in the epidemic season 2016/2017.
Output: Respiratory Infections with Particular Emphasis on Influenza Virus Activity in Persons Over 14 Years of Age in the Epidemic in Poland
Background: The current Ebola outbreak in West Africa and the large scale wild Polio virus outbreak in several countries are the top most issues among international public health and scientific communities' debates and concerns. These two outbreaks were judged to be declared as Public Health Emergency of International Concern (PHEIC) during 2014. This is the first time ever to have such circumstance of two PHEICs at the same time. Discussion: PHEIC, which has to be declared by WHO Director General after a recommendation of IHR Emergency Committee; is observed to start in countries with fragile health system and conflict areas. Then it rapidly spread to threaten the global public health. The year 2014 has uniquely witnessed declaration of two events as PHEIC according to IHR (2005); Polio and Ebola Virus Disease (EVD). Both outbreaks are caused by viruses such as H1N1 which was previously declared as PHEIC in 2009. Summary: Public Health Emergencies of International Concern in 2014 occurred in countries with weak health systems and conflicts and threatening the whole globe. International collaborative work is required to contain the event and to mobilize resources/capacities between countries. Moreover, public health surveillance systems as core capacity for IHR (2005) should be strengthened in all countries with focus on those with limited capacity and ongoing conflicts. The ultimate aim is timely detection of potential PHEIC events in the future along with early preparedness and response plans.
Output: Public Health Emergency of International Concern (PHEIC) has Declared Twice in 2014; Polio and Ebola at the Top
Background: The epidemiology of Mycoplasma pneumoniae (MP) and local dominant etiologies of pathogens that cause respiratory tract infections (RTIs) among central China children (≤14 years old) hospitalized are poorly understood. Methods: A total of 10,429 specimens were analyzed, and IgM antibodies against 9 respiratory pathogens including MP were detected using indirect immunofluorescence assay from serum. Results: It showed that 59.3% of the enrolled children were positive for at least 1 pathogen; highest detection rates included those between 3 and <6 years of age (70.4%), female (63.2%), and who were hospitalized in 2014 (80.9%). The most predominant pathogen was MP (45.6%), followed by Parainfluenza viruses (PIVs) (22.6%) and influenza B viruses (IFVB) (14.7%). Coinfection was observed in 2,907 specimens (27.9%); the coinfection combination containing MP and PIVs had the highest detection rate of 15%, followed by MP and IFVB as well as IFVB and PIVs. Conclusions: MP was the most commonly detected bacteria among hospitalized children, which should be included in the differential diagnosis for hospitalized children with RTI. These findings will contribute to the effective prevention and therapeutic approaches of pathogens among local children suffering from RTI.
Output: Viral and bacterial coinfection among hospitalized children with respiratory tract infections
The diagnostic performance of porcine epidemic diarrhea virus (PEDV) IgG and IgA ELISAs was evaluated using paired serum and meat juice samples collected from PEDV-negative (n = 50) and PEDV-inoculated pigs (n = 87). Serum samples were tested by PEDV (IgG, IgA) ELISAs using a procedure performed routinely at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were tested using PEDV serum IgG and IgA ELISA procedures as routinely performed at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were diluted 1:50 and conjugate concentrations were 1/20,000 for IgG and 1/3000 for IgA. Meat juice samples were tested using the serum PEDV IgG and IgA ELISAs, with modifications, i.e., meat juice samples were diluted 1:25 and conjugate concentrations were 1/40,000 for IgG and 1/10,000 for IgA. Receiver operator characteristic (ROC) curve analyses were used to estimate diagnostic sensitivities and specificities over a range of sample-to-positive (S/P) cutoffs. Consistent with previous reports, this study showed that the PEDV IgG and IgA meat juice ELISAs provided excellent diagnostic performance and suggest that meat juice recovered from samples collected at slaughter could be used in routine PEDV surveillance.
Output: Detection of porcine epidemic diarrhea virus (PEDV) IgG and IgA in muscle tissue exudate ("meat juice") specimens
Background and aims: Multiple issues in management of COVID have emerged, but confusion persists regarding rational interpretation. Aim of this brief review is to review these issues based on current literature. Methods: This is a narrative review with Pubmed and Google Scholar search till 23 March 2020. Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease. Results: We discuss evidence regarding role of chloroquine and hydroxychloroquine in treatment and prophylaxis, use of inhibitors of the renin angiotensin system, safety of ibuprofen, unusual clinical features like gastrointestinal symptoms and interpretation of tests for cardiac enzymes and biomarkers. Conclusions: While our conclusions on management of COVID-19 patients with co-morbidities are based on current evidence, however, data is limited and there is immediate need for fast track research.
Output: Original Article
Methods: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with earlystage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry. Results: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c ␣ chain (m/z 28 119) and an internal fragment of fibrinogen ␣-E chain (m/z 5908). Conclusions: Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.
Output: Serum Proteomic Fingerprints of Adult Patients with Severe Acute Respiratory Syndrome
The structure of the 5' GCGAUUUCUGACCGCUUUUUUGUCAG 3' RNA oligonucleotide was investigated using biochemical and chemical probes and nuclear magnetic resonance spectroscopy. Formation of a pseudoknot is indicated by the imino proton spectrum. Imino protons are observed consistent with formation of two helical stem regions; nuclear Overhauser enhancements between imino protons show that the two stem regions stack to form a continuous helix. In the stem regions, nucleotide conformations (3'-endo, anti) and internucleotide distances, derived from two-dimensional correlated, spectroscopy and two-dimensional nuclear Overhauser effect spectra, are characteristic of A-form geometry. The data suggest minor distortion in helical stacking at the junctions of stems and loops. The model of the pseudoknot is consistent with the structure originally proposed by Pleij et al. 1981; Heerschap, 1985; Hall et aZ., 1989) and Escherichia coli 5 S rRNA (122 nucleotides) Leontis 437
Output: Conformation of an RNA Pseudoknot
Highlights d N 1 -2 0 O-methylation is crucial to block RIG-I activation by viral and self RNA d Self-RNA exclusion is singularly governed by the conserved H830 in RIG-I d H830A alteration leads to indiscriminate recognition of endogenous RNA by RIG-I d Cellular N 1 -2 0 O-methyltransferase knockdown renders endogenous RNA stimulatory SUMMARY The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5 0 -triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5 0 -triphosphorylated, backbone modifications and the 5 0 -ppp-linked methylguanosine ( m7 G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5 0 -terminal nucleotide (N 1 ) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N 1 -2 0 O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N 1 -2 0 O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N 1 -2 0 O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2 0 O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N 1 -2 0 O-methylation in RIG-I tolerance of self-RNA.
Output: A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N 1 -2 0 O-Methylated Self RNA Article A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N 1 -2 0 O-Methylated Self RNA
The Influenza virus is a leading cause of respiratory disease in the United States each year. While the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. There are several methodologies that are used for detection; however problems such as decreased sensitivity and high rates of false-negative results may arise. There is a crucial need for an effective sample preparation technology that concentrates viruses at low abundance while excluding resident analytes that may interfere with detection. Nanotrap particles are hydrogel particles that are coupled to chemical dye affinity baits that bind a broad range of proteins and virions. Within minutes (<30 minutes), Nanotrap particles concentrate low abundant proteins and viruses from clinically complex matrices. Nanotrap particles with reactive red baits concentrated numerous respiratory viruses including various strains and subtypes of Influenza virus, Coronavirus, and Respiratory Syncytial Virus from saliva, nasal fluid swab specimens, and nasal aspirates. Detection was enhanced more than 10-fold when coupled to plaque assays and qRT-PCR. Importantly, Nanotrap particle can efficiently capture and concentrate multiple viral pathogens during a coinfection scenario. These results collectively demonstrate that Nanotrap particles are an important tool that can easily be integrated into various detection methodologies.
Output: Enhanced detection of respiratory pathogens with nanotrap particles
Coronaviruses most often infect the respiratory or intestinal tract. Transmissible gastroenteritis virus (TGEV), a group 1 coronavirus, infects the porcine small intestine. Piglets up to the age of 3 weeks die from diarrhea caused by the viral gastroenteritis unless they are protected by antibodies. In addition to the cellular receptor, porcine aminopeptidase N, the TGEV spike protein binds to sialic acid residues. We have shown that the sialic acid binding activity mediates the binding of TGEV to a mucin-like glycoprotein present in porcine brush border membranes. This was shown by performing a virus overlay binding assay with proteins obtained from brush border membranes by lectin precipitation. Because of the reactivity with specific lectins we assume that the recognized glycoprotein has the characteristics of a mucin.
Output: Identification of Sugar Residues Involved in the Binding of TGEV to Porcine Brush Border Membranes
It is complicated to measure the effects of various economic events on office markets within a nonparameter modeling framework. In response to this issue, a non-parametric statistical method-wavelet analysis is introduced in this study. Based on this innovative technique, we not only could detect the abrupt change points with a comparatively small data sample, but also could evaluate the impact from the abrupt change points by reconstructing the wavelet coefficient/de-noising the raw data, which had never been considered in previous studies of office markets. Our empirical results suggest that the wavelet reconstruction method, to some extent, makes it easier for the detection of the existence of structural change points. More interestingly, our findings also indicate that free market economies (i.e. Hong Kong and Singapore) are mainly influenced by the effects of global events, whereas the actual (net) impact on socialist economies (i.e. Beijing and Shanghai), depends on both the openness of the economies, and the magnitude of counter domestic forces put in place.
Output: Examining structural changes in Asian offices market