niryuu/sni-each-converted huggingface dataset:
After human coronaviruses OC43, 229E and NL63, human coronavirus HKU1 (HCoV-HKU1) is the fourth human coronavirus discovered. HCoV-HKU1 is a group 2a coronavirus that is still not cultivable. The G + C contents of HCoV-HKU1 genomes are 32%, the lowest among all known coronaviruses with complete genome sequences available. Among all coronaviruses, HCoV-HKU1 shows the most extreme codon usage bias, attributed most importantly to severe cytosine deamination. All HCoV-HKU1 genomes contain unique tandem copies of a 30-base acidic tandem repeat of unknown function at the N-terminus of nsp3 inside the acidic domain upstream of papain-like protease 1. Three genotypes, A, B and C, of HCoV-HKU1 and homologous recombination among their genomes, are observed. The incidence of HCoV-HKU1 infections is the highest in winter. Similar to other human coronaviruses, HCoV-HKU1 infections have been reported globally, with a median (range) incidence of 0.9 (0 -4.4) %. HCoV-HKU1 is associated with both upper and lower respiratory tract infections that are mostly selflimiting. The most common method for diagnosing HCoV-HKU1 infection is RT-PCR or real-time RT-PCR using RNA extracted from respiratory tract samples such as nasopharyngeal aspirates (NPA). Both the pol and nucleocapsid genes have been used as the targets for amplification. Monoclonal antibodies have been generated for direct antigen detection in NPA. For antibody detection, Escherichia coli BL21 and baculovirus- Viruses 2009, 1 58 expressed recombinant nucleocapsid of HCoV-HKU1 have been used for IgG and IgM detection in sera of patients and normal individuals, using Western blot and enzyme-linked immunoassay.
Output: More and More Coronaviruses: Human Coronavirus HKU1
To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail.
Output: DNA immunization as a technology platform for monoclonal antibody induction
One hundred and sixty-eight ganglia from 54 cattle aged 10 days to 10 years were examined microscopically. Samples from six autonomic ganglia and one sensory ganglion were represented. Thirteen animals were clinically normal and 41 were submitted for post-mortem examination. Neuronal vacuolation, spheroid formation, lipofuscin accumulation and central chromatolysis were observed sporadically and were of varying magnitude. Neuronal vacuolation and spheroid formation were not age-related changes, while lipofuscin accumulation was more common in older animals and central chromatolysis was more common in younger cattle. Nonsuppurative inflammation and neuronophagia were also common findings (23 out of 54 animals, 42.6%) in autonomic ganglia that did not contain herpesvirus DNA as determined by polymerase chain reaction. Renaut bodies, features of peripheral nerves, were most commonly noted in the vagus. None of the histopathological findings were related to any particular disease in which loss of autonomic nervous system function might be expected. Furthermore, all changes were as common in clinically normal animals as in animals with disease.
Output: A Histopathological Study of Bovine Ganglia
Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung disease, often goes unrecognized. We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children's Hospital, South Africa. Twelve children of Zimbabwean heritage aged 2.1-10.8 months were identified between 2012 and 2017. Repeated oral administration of plant-based oil for cultural reasons was reported by 10 of 11 caregivers. Cough (12/12), tachypnoea (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation. Chest computed tomography revealed ground-glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9). Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid-laden macrophages and extracellular lipid on Oil-Red-O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) coinfection. Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively. Clinicians should consider ELP in children with non-resolving pneumonia in settings with similar practices.
Output: Exogenous lipoid pneumonia: an important cause of interstitial lung disease in infants
Erosive polyarthritis was diagnosed in an 11-month-old neutered male Egyptian Mau-cross cat with concurrent glucocorticoid-responsive dermatitis. Clinical signs, synovial fluid analysis, serological tests and radiographic appearance could not differentiate between immune-mediated and infective arthritis. Mycoplasma gateae was isolated by strictly anaerobic culture of the synovial fluid. Treatment with Enrofloxacin led to a rapid improvement of the cat's condition. Two months later the cat was euthanased because of severe glomerulonephritis and direct Coombs' test positive anaemia, possibly caused by mycoplasma infection. M gateae could not be isolated at post-mortem examination.
Output: CASE REPORT Erosive polyarthritis associated with Mycoplasma gateae in a cat
Turkey coronavirus (TCoV) infection causes acute atrophic enteritis in the turkey poults, leading to significant economic loss in the U.S. turkey industry. Rapid detection, differentiation, and quantitation of TCoV are critical to the diagnosis and control of the disease. A specific one-step real-time reverse transcriptionpolymerase chain reaction (RRT-PCR) assay for detection and quantitation of TCoV in the turkey tissues was developed using a dual-labeled fluorescent probe. The fluorogenic probe labeled with a reporter dye (FAM, 6-carboxytetramethylrhodamin) and a quencher dye (AbsoluteQuencher TM ) was designed to bind to a 186 base-pair fragment flanked by the two PCR primers targeting the 3 end of spike gene of TCoV. The assay was performed on different avian viruses and bacteria to determine the specificity as well as serial dilutions of TCoV for the sensitivity. Three animal trials were conducted to further validate the assay. Ten-day-old turkey poults were inoculated orally with 100 EID 50 of TCoV. Intestinal tissues (duodenum, jejunum, ileum, cecum), feces from the cloacal swabs, or feces from the floor were collected at 12 h, 1, 2, 3, 5, 7, and/or 14 days post-inoculation (DPI). RNA was extracted from each sample and subjected to the RRT-PCR. The designed primers and probe were specific for TCoV. Other non-TCoV avian viruses and bacteria were not amplified by RRT-PCR. The assay was highly sensitive and could quantitate between 10 2 and 10 10 copies/l of viral genome. The viral RNA in the intestine segments reached the highest level, 6 × 10 15 copies/l, in the jejunum at 5 DPI. Eighty-four intestine segments assayed by the developed RRT-PCR and immunofluorescence antibody assay (IFA) revealed that there were 6 segments negative for TCoV by both assays, 45 positive for TCoV by IFA, and 77 positive for TCoV by RRT-PCR. Turkey coronavirus was detected in the feces from the cloacal swabs or floor 1-14 DPI; however, the viral RNA load varied among different turkey poults at different intervals from different trials. The highest amount of viral RNA, 2.8 × 10 10 copies/l, in the feces was the one from the cloacal swab collected at 1 DPI. The average amount of TCoV RNA in the cloacal fecal samples was 10 times higher than that in the fecal droppings on the floor. Taken together, the results indicated that the developed RRT-PCR assay is rapid, sensitive, and specific for detection, differentiation, and quantitation of TCoV in the turkey tissues and should be helpful in monitoring the progression of TCoV induced acute enteritis in the turkey flocks.
Output: Specific real-time reverse transcription-polymerase chain reaction for detection and quantitation of turkey coronavirus RNA in tissues and feces from turkeys infected with turkey coronavirus
Autophagy is a common strategy for cell protection; however, some viruses can in turn adopt cellular autophagy to promote viral replication. Zika virus (ZIKV) is the pathogen that causes Zika viral disease, and it is a mosquito-borne virus. However, its pathogenesis, especially the interaction between ZIKV and target cells during the early stages of infection, is still unclear. In this study, we demonstrate that infecting human umbilical vein endothelial cells (HUVEC) with ZIKV triggers cellular autophagy. We observed both an increase in the conversion of LC3-I to LC3-II and increased accumulation of fluorescent cells with LC3 dots, which are considered to be the two key indicators of autophagy. The ratio of LC3-II/GAPDH in each group was significantly increased at different times after ZIKV infection at different MOIs, indicating that the production of lipidated LC3-II increased. Moreover, both the ratio of LC3-II/GAPDH and the expression of viral NS3 protein increased with increasing time of viral infection. The expression level of p62 decreased gradually from 12 h post-infection. Expression profile of double fluorescent protein labelling LC3 indicated that the autophagy induced by ZIKV infection was a complete process. We further investigated the role of autophagy in ZIKV replication. We demonstrated that either the treatment with inhibitors of autophagosomes formation or short hairpin RNA targeting the Beclin-1 gene, which is critical for the formation of autophagosomes, significantly reduced viral production. Taken together, our results indicate that ZIKV infection induces autophagy of HUVEC, and inhibition of ZIKV-induced autophagy restrains viral replication.
Output: Zika Virus Induces Autophagy in Human Umbilical Vein Endothelial Cells
Background: Clinical laboratory workers face biohazard such as needlestick injury and occupational infection on a daily basis. In this study, we examined self-reported frequency of occupational infection and needlestick injury among the clinical laboratory workers in Al-Madinah, Saudi Arabia. Methods: A total of 234 clinical laboratory workers were recruited from private and government health sectors to answer a self-administered questionnaire that was prepared to achieve the aims of the study. Results: The results showed that approximately 33% of the sample had an experienced occupational infection while 24% had experienced a needlestick injury. Approximately, 49% reported that they always recap needle after use, whereas 15% reported doing that most of the times. Occupational infection, needlestick injury and recapping needles after use were associated with lack of training on biosafety (P < 0.05). Conclusion: The frequency of occupational infection and needlestick injury among clinical laboratory workers in Al-Madinah is high. Interventions related to biosafety and infection control and the use of needlestick prevention devices might be useful in lowering such frequency.
Output: Occupational infection and needle stick injury among clinical laboratory workers in Al-Madinah city, Saudi Arabia
Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R 0 ) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R 0 . 1) is brought under control after a delay. The coefficient of variation of final outbreak size in the subcritical case (R 0 , 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV . 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.
Output: Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases
The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools. To overcome these limitations, we describe the use of an incremental meta-docking approach for structural prediction of pMHC complexes. Previous methods applied in this context used specific constraints to reduce the complexity of this prediction problem, at the expense of generality. Our strategy makes no assumption and can potentially be used to predict binding modes for any pMHC complex. Our method has been tested in a re-docking experiment, reproducing the binding modes of 25 pMHC complexes whose crystal structures are available. This study is a proof of concept that incremental docking strategies can lead to general geometry prediction of pMHC complexes, with potential applications for immunotherapy against cancer or infectious diseases.
Output: General Prediction of Peptide-MHC Binding Modes Using Incremental Docking: A Proof of Concept
PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.
Output: PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs
TBX2 and TBX3 are members of the T-box family of transcription factors, which are implicated in embryonic development. Unlike most members of the T-box family, TBX2 and TBX3 are the only mammalian T-box factors which function as transcriptional repressors, mediated by the repression domain in the C-terminal. In addition to a role in development, recent evidence suggests that TBX2 and TBX3 are overexpressed in a number of cancers, including melanoma, breast, liver, lung, pancreas, ovarian, and cervical cancers. However, there is little information about the mechanisms for how these T-box genes contribute to tumorigenesis. Upregulation of TBX2 and TBX3 suppresses the expression of p14 ARF and p21 CIP1 and promotes bypass of senescence through inactivation of p53 pathway. TBX2 functionally interacts with pRb, and pRb modulates TBX2 functional specificity. In addition, TBX2 is a player of Wnt signaling while TBX3 is a downstream target of the Wnt/beta-catenin pathway, and overexpression of TBX2 and TBX3 represses the expression of Ecadherin, which is demonstrated to be a prerequisite for epithelial tumor cell invasion. Moreover, TBX2 is shown to interact with EGR1 to block multiple downstream tumor suppressors. Here, we review the current knowledge on TBX2 and TBX3 in tumorigenesis and prospect their special value for development of targetbased anticancer drugs.
Output: TBX2 and TBX3: The special value for anticancer drug targets
The severe acute respiratory syndrome coronavirus (SARS-CoV) first emerged in 2003, causing the SARS epidemic which resulted in a 10% fatality rate. The advancements in metagenomic techniques have allowed the identification of SARS-like coronaviruses (SL-CoVs) sequences that share high homology to the human SARS-CoV epidemic strains from wildlife bats, presenting concrete evidence that bats are the origin and natural reservoir of SARS-CoV. The application of reverse genetics further enabled that characterization of these bat CoVs and the prediction of their potential to cause disease in humans. The knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.
Output: Understanding bat SARS-like coronaviruses for the preparation of future coronavirus outbreaks -Implications for coronavirus vaccine development
Detection and characterisation of the canine parvovirus (CPV-2) strains that are currently circulating are essential for the understanding of viral evolution and the development of measures to control its spread. In the present study, stool samples from 144 dogs were analysed by polymerase chain reaction (PCR) for CPV-2, and 29.2% (42/144) of them were positive. From the 42 positive strains, 71.4% (30) of the dogs had signs of haemorrhagic gastroenteritis. The sequencing of the 583 bp fragment of the VP2 gene from the positive strains identified 78.6% (33/42) of them as type 2c, 19% (8/42) as type 2b and 2.4% (1/42) as type 2a. A phylogenetic analysis of the variants circulating in the canine population of Brazil showed that they are very similar to those found in other countries and type 2c has become the predominant type circulating in Brazil.
Output: Typing of canine parvovirus strains circulating in Brazil between 2008 and 2010
Background: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. Methods and Findings: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. Conclusion: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.
Output: Isolation Facilities for Highly Infectious Diseases in Europe -A Cross-Sectional Analysis in 16 Countries
Ethnopharmacological relevance: Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicine, was known as Jin Yin Hua (Chinese: ), Ren Dong and Japanese honeysuckle. It was taken to treat the exopathogenic wind-heat, epidemic febrile diseases, sores, carbuncles and some infectious diseases. At the same time, Lonicera japonica could be used as healthy food, cosmetics, ornamental groundcover, and so on. Aim of the review: The present paper reviewed the ethnopharmacology, the biological activities, toxicology and phytochemistry of Lonicera japonica. Materials and methods: Information on Lonicera japonica was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI and Web of Science) and libraries. Additionally, information also was obtained from some local books and brilliant scholars on ethnopharmacology. Results: More than 140 chemical compounds have been isolated, and the main compositions are essential oils, organic acids and flavones, etc. Lonicera japonica and its active principles possess wide pharmacological actions, such as anti-inflammatory, antibacterial, antiviral, antioxidative and hepatoprotective activities. Conclusions: As an important traditional Chinese medicine, further studies on Lonicera japonica can lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attentions.
Output: Lonicera japonica Thunb.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine
Optometrists are uniquely placed in the health care field because they provide both services as well as goods to patients. In the event of an influenza pandemic, optometrists may be challenged with a host of issues, including impediments to clinical patient care, manufacture and delivery of ophthalmic devices, and maintaining business continuity and infection control. OVERVIEW: This report reviews pandemic influenza, the effect of a pandemic event on business survival, and response measures for the primary eye care provider. The ethical and legal issues surrounding control of a pandemic influenza and the prospect of telemedicine as a form of social distancing are also discussed. CONCLUSIONS: Knowledge of the pharmacologic and nonpharmacologic measures to control a pandemic influenza will help prepare the eye care provider for addressing challenges to patient care and business continuity in the face of a highly contagious disease. Understanding the legal and ethical issues that arise during a pandemic event will help optometrists make informed choices as health care professionals and as citizens. Optometry 2007;78:629-643
Output: The prospect of pandemic influenza: Why should the optometrist be concerned about a public health problem?
Background: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches. We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories. Conclusions: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.
Output: Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species
Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an 'extended incubation phase' PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development.
Output: Characterization of Neutralizing Profiles in HIV-1 Infected Patients from whom the HJ16, HGN194 and HK20 mAbs were Obtained
MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTEH) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells. To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches. We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326-349 and 388-410, with critical residues F 326 , T 328 , N 333 , V 388 , G 389 , P 390 , E 392 , I 408 , and N 410 . Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates. Searching the National Center for Biotechnology Information GenBankH database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain. Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant. Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA. In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA. Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA. Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA.
Output: The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA
Aptamers are short, single-stranded DNA, RNA, or synthetic XNA molecules that can be developed with high affinity and specificity to interact with any desired targets. They have been widely used in facilitating discoveries in basic research, ensuring food safety and monitoring the environment. Furthermore, aptamers play promising roles as clinical diagnostics and therapeutic agents. This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine. The limitations and future directions of aptamers in target specific delivery and real-time detection are also discussed.
Output: molecules Recent Advances in Aptamer Discovery and Applications
Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.
Output: Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus
Avian infectious bronchitis virus (IBV), which causes respiratory disease in infected birds, belongs to coronavirus group 3. IBV encodes 15 nonstructural proteins (nsp2-nsp16) which play crucial roles in RNA transcription and genome replication. Nonstructural protein 9 (nsp9) has been identified as a protein that is essential to viral replication because of its single-stranded RNAbinding ability. The gene segment encoding IBV nsp9 has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted X-rays to 2.44 Å resolution. They belonged to the cubic space group I432, with unit-cell parameters a = b = c = 123.4 Å , = = = 90 . The asymmetric unit appeared to contain one molecule, with a solvent content of 62% (V M = 3.26 Å 3 Da À1 ). # 2010 International Union of Crystallography All rights reserved crystallization communications 708 Ma et al. Infectious bronchitis virus nonstructural protein 9 Acta Cryst. (2010). F66, 706-708 Figure 2 A typical diffraction pattern of an IBV nsp9 crystal collected on a Rigaku R-AXIS IV ++ image-plate detector.
Output: Structural Biology and Crystallization Communications Crystallization and preliminary X-ray diffraction studies of infectious bronchitis virus nonstructural protein 9
a b s t r a c t RFID technology meets identification and tracking requirements in healthcare environments with potential to speed up and increase reliability of involved processes. Due to this, high expectations for this integration have emerged, but hospital and medical centers interested in adoption of RFID technology require prior knowledge on how to squeeze RFID capabilities, real expectations and current challenges. In this paper, we show our lab tested solutions in two specific healthcare scenarios. On the one hand, we analyze the case of a medical equipment tracking system for healthcare facilities enabling both real-time location and theft prevention. Worth-noting aspects such as possible EMI interferences, technology selection and management of RFID data from hospital information system are analyzed. Lab testing of system reliability based on passive UHF RFID is provided for this case. On the other hand, we analyze and provide a solution for care and control of patients in a hospital based on passive HF RFID with the result of a fully functional demonstrator. Our prototype squeezes RFID features in order to provide a backup data source from patient's wristband. It also provides an offline working mode aiming to increase application reliability under network fail down and therefore, improving patient's safety. Considerations regarding lessons learned and challenges faced are exposed.
Output: Real-time location and inpatient care systems based on passive RFID
Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV.
Output: Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins 4
Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC 50 values ranging from 3.9 to 20.0 lM and selectivities >10. Three sulfonamide compounds with EC 50 values <12 lM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.
Output: A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus
This study investigated the heterogeneity and plasticity of porcine alveolar macrophages (PAM) and pulmonary interstitial macrophages (IM) isolated from healthy pigs, including phenotype, function and gene expression. Dynamic changes of nitric oxide (NO) levels secreted by PAM and IM with stimulation of different doses of lipopolysaccharide (LPS) were investigated by Griess method, and the viability of the PAM and IM cells was investigated by MTT assay. Flow cytometry, fluorescence quantitative PCR and ELISA techniques were used to measure cell phenotype, gene expression and cytokine secretion, respectively. The PAM and IM cells in normal healthy pigs showed heterogeneity with 95.42±1.51% and 31.99±5.84% of CD163+ macrophage, respectively. The NO level in IM was significantly higher versus PAM after LPS treatment. Consistently, the ratio of Arg I/iNOS in IM was much lower than that in PAM, suggesting that the PAM belong to M2 macrophages and the IM belong to M1 macrophages. The PAM and IM cells in normal healthy pigs also showed plasticity. The Arg I/iNOS ratio and TIMP1/MMP12 ratio were significantly decreased in LPS-or LPS+IFNγ-treated PAM and IM, suggesting that cells were polarized towards M1 macrophages under LPS or LPS+IFNγ stimulation. On the contrary, IL-4 and IL-13 stimulation on PAM and IM lead to M2 polarization. A similar result was found in IL-1β gene expression and TNFα secretion. In conclusion, porcine macrophages have shown heterogeneity and plasticity on polarization under the stimulation of LPS, IFNγ, IL-4 and IL-13.
Output: Heterogeneity and plasticity of porcine alveolar macrophage and pulmonary interstitial macrophage isolated from healthy pigs in vitro
Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by . CC-BY-NC 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Network-based Drug Repurposing for Human Coronavirus
The rapid diffusion of social media is ushering in a new era of crisis communication. To enhance our understanding of the social-mediated dialogue between organizations and their publics in crises of China, this study conducts a content analysis of 61 relevant journal articles published in 2006-2018. Results of this research present an overview of ongoing research trends such as theoretical frameworks and methodological preferences. This research also explores how the unique Chinese social media characteristics affect the dialogue between types of organizations and their publics. Contextual factors such as face and favor, relationship (Guanxi) and sentiment (Renqing), and the centralized political system that may facilitate/inhibit dialogue in crises of China are identified as well. Finally, this study suggests promising new directions such as a scholarly assessment tool for the social-mediated crisis communication research in China.
Output: The social-mediated crisis communication research: Revisiting dialogue between organizations and publics in crises of China
In response to WHO raising the infl uenza pandemic alert level from phase fi ve to phase six, health offi cials around the world are carefully reviewing pandemic mitigation protocols. School closure (also called class dismissal in North America) is a non-pharmaceutical intervention that is commonly suggested for mitigating infl uenza pandemics. Health offi cials taking the decision to close schools must weigh the potential health benefi ts of reducing transmission and thus case numbers against high economic and social costs, diffi cult ethical issues, and the possible disruption of key services such as health care. Also, if schools are expected to close as a deliberate policy option, or just because of high levels of staff absenteeism, it is important to plan to mitigate the negative features of closure. In this context, there is still debate about if, when, and how school closure policy should be used. In this Review, we take a multidisciplinary and holistic perspective and review the multiple aspects of school closure as a public health policy. Implications for the mitigation of the swine-origin infl uenza A H1N1 pandemic are also discussed. Lancet Infect Dis 2009; 9: 473-81 MRC Centre for Outbreak Analysis and Modelling, (A Tegnell MD); Chargé de mission auprès du délégué interministériel à la lute contre la grippe aviaire,
Output: Review Closure of schools during an infl uenza pandemic
The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC ¼ 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC ¼ 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homology-reduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at:
Output: Predicting linear B-cell epitopes using string kernels
Segmental and focal pathological changes were found in the glomeruli and tubules of postoperative renal-biopsy specimens from seven cases of clinically confirmed endemic (Balkan) nephropathy. In the glomeruli, there was mesangial reaction and segmental thickening of the basement membrane with subendothelial and membranous depositions. In the tubules there was spongiform degeneration and fusion of cells. In all the cells of the nephron numerous cytoplasmic vesicles containing free and budding particles (80-200 nm) were found. These particles had the characteristics of a coronavirus. Balkan
Output: Presse m&eacute;d. 1975, 4, 1211. 11. Smith
Recent epidemics of West Nile virus (WNV) around the world have been associated with significant rates of mortality and morbidity in humans. To develop standard WNV diagnostic tools that can differentiate WNV from Japanese encephalitis virus (JEV), four monoclonal antibodies (MAbs) specific to WNV envelope (E) protein were produced and characterized by isotyping, reactivity with denatured and native antigens, affinity assay, immunofluorescence assay (IFA), and epitope competition, as well as cross-reactivity with JEV. Two of the MAbs (6A11 and 4B3) showed stronger reactivity with E protein than the others (2F5 and 6H7) in Western blot analysis. 4B3 could bind with denatured antigen, as well as native antigens in indirect ELISA, flow cytometry analysis, and IFA; whereas 2F5 showed highest affinity with native antigen. 4B3 and 2F5 were therefore used to establish an antigen capture-ELISA (AC-ELISA) detection system. The sensitivity of this AC-ELISA was 3.95 TCID 50 /0.1 ml for WNV-infected cell culture supernatant. Notably, these MAbs showed no cross-reactivity with JEV, which suggests that they are useful for further development of highly sensitive, easy handling, and less time-consuming detection kits/tools in WNV surveillance in areas where JEV is epidemic.
Output: Characterization and application of monoclonal antibodies specific to West Nile virus envelope protein