niryuu/sni-each-converted huggingface dataset:
Bovine renal brush-border membrane vesicle aminopeptidase N at various stages of purity was treated with two bifunctional cross-linking agents. A pattern of emergence of higher molecular weight forms was observed. By using a cleavable cross-linker, aminopeptidase N was shown to cross-link both to itself and to its breakdown products as well as to dipeptidyl peptidase IV. Using this technique it was possible to identify three of the breakdown products as 45 kDa, 66 kDa and 95 kDa peptides. N-terminal amino acid sequence analysis was used to define the precise cleavage points for the bovine renal aminopeptidase N breakdown products. The short amino acid sequences obtained show strong sequence similarity with the human intestinal and rat kidney aminopeptidase N.
Output: The oligomeric structure of renal aminopeptidase N from bovine brush-border membrane vesicles
Respiratory syncytial virus (RSV) is a significant cause of morbidity in humans. To date, no effective treatments exist and current prophylactic therapy access is limited and is only w50% effective. To attenuate the risk of RSV infection, we hypothesized that bioengineering of either the virus particle or host cell via the covalent grafting of methoxypoly(ethylene glycol) [mPEG] would prevent infection. To this end, the anti-viral effects of grafting concentration, linker chemistry and polymer length on RSV infection was assessed. For viral modification, short chain polymers (2 kDa) were significantly more effective than long chain (20 kDa) polymers. In contrast, modification of host cells with small polymers provided no (w0%) protection while long chain polymers effectively prevented infection. For example, at 48 hours post-infection at a multiplicity of infection of 0.5 and grafting concentrations of 5, 7.5, and 15 mM, 20 kDa mPEG decreased infection by 45, 83, and 91%, respectively. Importantly, both viral and host cell PEGylation strategies were able to provide near complete protection against RSV infection of both non-polarized and polarized cells. In conclusion, mPEGmodification of either RSV or the host cell is a highly effective prophylactic strategy for preventing viral infection.
Output: The effect of grafted methoxypoly(ethylene glycol) chain length on the inhibition of respiratory syncytial virus (RSV) infection and proliferation
The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkageselective recognition of Ub chains by Ub-binding domain (UBD)containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb. We here identify that this linkageselective binding is mediated by a single MIU motif (MIU2) in MINDY-1. The crystal structure of MIU2 in complex with K48-linked polyubiquitin chains reveals that MIU2 on its own binds to all three Ub moieties in an open conformation that can only be accommodated by K48-linked triUb. The weak Ub binder MIU1 increases overall affinity of the tMIU for polyUb chains without affecting its linkage selectivity. Our analyses reveal new concepts for linkage selectivity and polyUb recognition by UBDs.
Output: A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains
Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain-Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage.
Output: Citation: A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue
Attaching and effacing Escherichia coli are involved in diarrhea in 2 to 8-week old calves. The virulence factors of these bacteria include: (i) the secretion of proteins (i.e. EspB) involved in microvilli effacement, (ii) the production of the intimin, a 94 kDa outer membrane protein encoded by the eaeA gene and involved in the intimate attachment of bacteria to epithelial cell and (iii) the production of verotoxins: VT1 and/or VT2. We investigated the presence and the pathotype of these strains in several calf populations by colony hybridization or by genetic amplification. Using the colony hybridization method we showed first that only 5% of calves who died from diarrhea presented EaeA E. coli strains and secondly that 19% of healthy calves showed an asymptomatic carriage. However, using colony hybridization and genetic amplification, we identified EaeA strains in 91% of calves living in farms with recurrent diarrhea problems. In 66% of the calves, there was a correlation between the presence of AEEC and diarrhea. At the pathotype level, most of the EaeA isolates were negative for VT probes. In VT bacteria, the majority were VT1. The number of VT positive bacteria was significantly higher in calves who died from diarrhea than in healthy or sick calves. This underlined the aggravating role of verotoxins in the disease. Moreover, only 25% of the bovine AEEC were positive with the EaeB probe. Surprisingly, the proportion of EaeB strains was significantly higher in healthy calves than in other populations. # 1998 Elsevier Science B.V. All rights reserved.
Output: Prevalence and molecular typing of attaching and effacing Escherichia coli among calf populations in Belgium
We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.
Output: Optimal design and validation of antiviral siRNA for targeting HIV-1
Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models. First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options. This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks. PLoS Medicine | www.plosmedicine.org July 2005 | Volume 2 | Issue 7 | e174 0621 Open access, freely available online PL o S MEDICINE
Output: Appropriate Models for the Management of Infectious Diseases
To analyze pathogenic species in bats from southeast coastal regions of China, we performed metagenomic sequencing technology for high throughput sequencing of six sentinels from southeast coastal area of China. We obtained 5,990,261 high quality reads from intestine and lung tissue of 235 bats, including 2,975,371 assembled sequences. 631,490 reads predicted overlapping sequences for the open reading frame (ORF), which accounts for 2.37% of all the sequences (15,012/631,490). Further, the acquired virus sequences were classified into 25 viral families, including 16 vertebrate viruses, four plant viruses and five insect viruses. All bat samples were screened by specific PCR and phylogenetic analysis. Using these techniques, we discovered many novel bat viruses and some bat viruses closelyrelated to known human/animal pathogens, including coronavirus, norovirus, adenovirus, bocavirus, astrovirus, and circovirus. In summary, this study extended our understanding of bats as the viral reservoirs. Additionally, it also provides a basis for furher studying the transmission of viruses from bats to humans. Bats belong to the order Chiroptera, and are the second largest order of mammals after rodents. This order includes 19 families and 962 species distributed across the globe 1 . More than 130 kinds of viruses have been detected in bats, including more than 60 species of zoonotic viruses which are highly pathogenic in humans 2 , such as severe acute respiratory syndrome (SARS)-like coronavirus (SL-CoV), Ebola virus, Nipah virus, and Hendra virus 3-6 . In 2002, SARS outbreak in China infected more than 8,000 people worldwide and killed at least 800 people. Chinese horseshoe bats were proved to be the natural reservoirs of SARS-CoV and that intermediate hosts may not be necessary for direct human infection by a bat hosting SL-CoV 7 . Similarly, Middle East respiratory syndrome (MERS)-associated coronavirus were detected in bats, and required dipeptidyl peptidase 4 cell receptors for its invasion into host cells 8 . It seems likely that bats might act as natural hosts which critical roles in viral iner-host transmission. In the last five years, the use of second-generation sequence technology allowed us to elucidate a flood of viruses, like SARS-CoV, hepatitis B virus, rotavirus and other important viruses 9-11 . In 2010, meta-genomic analysis was conducted for the first time, following the second generation sequencing of oral swab and faecal samples from 41 bats of three common North American bat species. The results showed that sample pools contained strong matches to at least three novel group of CoVs, and large numbers of insect and plant virus sequences were identified 12 . One bat virome analysis conducted by Ge et al. on fecal samples of bats from six locations in China 13 , and 97 contigs were found to be related to eukaryotic viruses, including coronavirus. Then, one bat virome analysis in Myanmar conducted by He et al. has identified many new mammalian viruses of Myanmar bats 14 , showing
Output: Virome analysis for identification of novel mammalian viruses in bats from Southeast China OPEN
This study examines both numerically and experimentally the micro-environmental conditions in public transportation buses. A Computational Fluid Dynamics (CFD) model was developed and experimentally validated. The developed CFD model was used to calculate the spatial distributions of the mean age and mean residual lifetime of air in the bus environment and evaluate the efficiency of the bus ventilation system. Additionally, the passengers' exposures to a variety of environmental conditions were experimentally monitored in "real world" field campaigns using the Harvard University shuttle bus system. Real time continuous monitoring systems were used to assess indoor environmental quality in the buses. It was found that CO levels were very low, while the levels of particulate matter varied and were influenced by the ambient air penetrated into the bus through the operation of the doors and the ventilation system. The CO 2 level was found elevated and greatly affected by occupancy conditions. The elevated CO 2 level indicates that the current bus ventilation is insufficient to dilute air pollutants in the bus especially under heavy occupancy conditions. This lack of sufficient ventilation indicates an elevated risk for airborne transmitted diseases in such a popular public transportation system.
Output: Experimental and numerical investigation of micro-environmental conditions in public transportation buses
Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P < 0.05); while variants of CXCL11 showed moderate significance of association (P = 0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, ''CCCCA'' of gene CXCL10 and ''AGTTTAC'' of CXCL11 were found to be significantly associated with vascular leakage (P = 0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection. Ó
Output: Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia
Background: Mouse B78 cells and Chinese hamster ovary (CHO) cells are important to the study of HSV-1 entry because both are resistant to infection at the level of viral entry. When provided with a gD-receptor such as nectin-1, these cells support HSV-1 entry by an endocytosis pathway. Treating some viruses bound to cells with the fusogen polyethylene glycol (PEG) mediates viral fusion with the cell surface but is insufficient to rescue viral entry. It is unclear whether PEG-mediated fusion of HSV with the plasma membrane of B78 or CHO cells results in successful entry and infection. Findings: Treating HSV-1 bound to B78 or CHO cells with PEG allowed viral entry as measured by virus-induced beta-galactosidase activity. Based on the mechanism of PEG action, we propose that entry likely proceeds by direct fusion of HSV particles with the plasma membrane. Under the conditions tested, PEG-mediated infection of CHO cells progressed to the level of HSV late gene expression, while B78 cells supported HSV DNA replication. We tested whether proteolysis or acidification of cell-bound virions could trigger HSV fusion with the plasma membrane. Under the conditions tested, mildly acidic pH of 5-6 or the protease trypsin were not capable of triggering HSV-1 fusion as compared to PEG-treated cell-bound virions. Conclusions: B78 cells and CHO cells, which typically endocytose HSV prior to viral penetration, are capable of supporting HSV-1 entry via direct penetration. HSV capsids delivered directly to the cytosol at the periphery of these cells complete the entry process. B78 and CHO cells may be utilized to screen for factors that trigger entry as a consequence of fusion of virions with the cell surface, and PEG treatment can provide a necessary control.
Output: Polyethylene glycol-mediated fusion of herpes simplex type 1 virions with the plasma membrane of cells that support endocytic entry
Background: The spread of pathogens via the airborne route is often underestimated, and little is known about the extent to which airborne microbial contamination levels vary throughout the day and night in hospital facilities. Aims: To evaluate airborne contamination levels within intensive care unit (ICU) isolation rooms over 10e24-h periods in order to improve understanding of the variability of environmental aerial bioburden, and the extent to which ward activities may contribute. Methods: Environmental air monitoring was conducted within occupied and vacant inpatient isolation rooms. A sieve impactor sampler was used to collect 500-L air samples every 15 min over 10-h (08:00e18:00 h) and 24-h (08:00e08:00 h) periods. Samples were collected, room activity was logged, and bacterial contamination levels were recorded as colony-forming units (cfu)/m 3 air. Findings: A high degree of variability in levels of airborne contamination was observed across all scenarios in the studied isolation rooms. Air bioburden increased as room occupancy increased, with air contamination levels highest in rooms occupied for the longest time during the study (10 days) (mean 104.4 cfu/m 3 , range 12e510 cfu/m 3 ). Counts were lowest in unoccupied rooms (mean 20 cfu/m 3 ) and during the night. Conclusion: Peaks in airborne contamination were directly associated with an increase in activity levels. This study provides the first clear evidence of the extent of variability in microbial airborne levels over 24-h periods in ICU isolation rooms, and found direct correlation between microbial load and ward activity.
Output: Continuous monitoring of aerial bioburden within intensive care isolation rooms and identification of high-risk activities
Our ability to uncover complex network structure and dynamics from data is fundamental to understanding and controlling collective dynamics in complex systems. Despite recent progress in this area, reconstructing networks with stochastic dynamical processes from limited time series remains to be an outstanding problem. Here we develop a framework based on compressed sensing to reconstruct complex networks on which stochastic spreading dynamics take place. We apply the methodology to a large number of model and real networks, finding that a full reconstruction of inhomogeneous interactions can be achieved from small amounts of polarized (binary) data, a virtue of compressed sensing. Further, we demonstrate that a hidden source that triggers the spreading process but is externally inaccessible can be ascertained and located with high confidence in the absence of direct routes of propagation from it. Our approach thus establishes a paradigm for tracing and controlling epidemic invasion and information diffusion in complex networked systems. ½S i ðt 2 Þ þ S i ðt 6 Þ=2 and hS i ðt 2 þ 1Þi ¼ ½S i ðt 12 Þ þ S i ðt 14 Þ=2 based on the remaining strings marked in different colours (see Methods for more details). CST can be used to reconstruct the neighbouring vector X of node 2 from Y and U from Y ¼ U . X.
Output: ARTICLE Reconstructing propagation networks with natural diversity and identifying hidden sources
The intracellular disposition of the carboxy-terminus tail of rabbit lactase-phlorizin hydrolase (LPH) is demonstrated, using a specific phospborylation of Ser 1916 by protein kinase A (PKA). This phosphorylation is shown to occur not only in vitro (with pure LPH and pure catalytic subunit of PKA), but also in an organ culture of the small intestine. Cholera toxin, which is known to act in vivo on the membranes of the small intestine, with severe clinical consequences, and to elevate the intracellular cyclic AMP of enterocytes, is shown to enhance significantly the phosphorylation of LPH in intact cells grown as an organ culture. These findings establish the cytosolic orientation of the carboxyterminus tail of LPH in situ, and raise the possibility that the tail itself and its phosphorylation by PKA may have a physiological or physiopatbological significance.
Output: Disposition of the hydrolase elucidated carboxy-terminus tail of rabbit lactase-phlorizin by phosphorylation with protein kinase A in vitro and in tissue culture
hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoproteinbased indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%-42.9% of cave-dwelling bats and 0.6%-7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a viruslike particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV.
Output: Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses
Background and objectives: Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods: Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results: In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion: Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.
Output: Revista Clínica Española Clinico-epidemiological characteristics of acute respiratory infections by coronavirus OC43, NL63 and 229E ଝ PALABRAS CLAVE
Background: Viral aetiologies are the most common cause of central nervous system (CNS) infections. Approximately one-half of CNS infections remain of undetermined origin. High-throughput sequencing (HTS) brought new perspectives to CNS infection investigations, allowing investigation of viral aetiologies with an unbiased approach. HTS use is still limited to specific clinical situations. Objectives: The aim of this review was to evaluate the contribution and pitfalls of HTS for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis in CNS patient samples. Sources: PubMed was searched from 1 January 2008 to 2 August 2018 to retrieve available studies on the topic. Additional publications were included from a review of full-text sources. Content: Among 366 studies retrieved, 29 used HTS as a diagnostic technique. HTS was performed in cerebrospinal fluid and brain biopsy samples of 307 patients, including immunocompromised, immunocompetent paediatric, and adult cases. HTS was performed retrospectively in 18 studies and prospectively in 11. HTS led to the identification of a potential causal virus in 41 patients, with 11 viruses known and ten not expected to cause CNS infections. Various HTS protocols were used. Implications: The additional value of HTS is difficult to quantify because of various biases. Nevertheless, HTS led to the identification of a viral cause in 13% of encephalitis, meningoencephalitis, and meningitis cases in which various assays failed to identify the cause. HTS should be considered early in clinical management as a complement to routine assays. Standardized strategies and systematic studies are needed for the integration of HTS in clinical management. M.-C. Zanella, Clin Microbiol Infect 2019;25:422
Output: High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal
Brefeldin A (BFA), a unique fungal metabolite of a 13-membered lactone ring, exhibits various biological actions, including antitumor, antifungal and antiviral activities. In the present study, mouse LB cells were treated with various concentrations of interferon (IFN) and/or BFA overnight and infected with encephalomyocarditis virus (EMCV) after removal of IFN and BFA. Doses of BFA which neither inhibit the metabolism of the cell nor the infectivity of EMCV, decreased the IFN-induced antiviral activity against EMCV as demonstrated by virus titer from supernatants. Since 2-5A synthetase and double-stranded RNA (dsRNA)-dependent protein kinase (PKR) have been suggested to be involved in the antiviral action of IFN against EMCV, their activities were investigated in LB cells after BFA treatment. Northern blot analysis and in situ hybridization showed a decrease (2-3-fold) in the mRNA of 2'-5' oligoadenylate (2-5A) synthetase after BFA treatment. BFA also inhibited the activity of 2-5A synthetase, 2-5A dependent RNase i and phosphorylation of PKR in cellular extracts, indicating that BFA may be exerting its inhibitory effect both at theltranscriptional and post-transcriptional levels. This study reports a new biological action of BFA, demonstrating that BFA antagonized the antiviral action of IFN by inhibiting IFN-induced enzymatic pathways. These studies also suggest that both 2-5A and PKR are important in the antiviral activity of IFN against EMCV.
Output: Brefeldin A inhibits the antiviral action of interferon against encephalomyocarditis virus
The Mad1-Mad2 heterodimer is the catalytic hub of the spindle assembly checkpoint (SAC), which controls mitosis through assembly of a multi-subunit anaphase inhibitor, the mitotic checkpoint complex (MCC) [1, 2] . Mad1-Mad2 first catalyzes MCC assembly at interphase nuclear pores [3] , then migrates to kinetochores at nuclear envelope breakdown (NEBD) and resumes MCC assembly until bipolar spindle attachment is complete [1, 2] . There is significant debate about the factor(s) involved in targeting Mad1-Mad2 to kinetochores in higher eukaryotes [4] [5] [6] [7] [8] [9] . Through gene editing and livecell imaging, we found that the human Rod-Zw10-Zwilch (RZZ) complex is dispensable for cell viability and initial recruitment of Mad1-Mad2 to kinetochores at NEBD, but then becomes necessary to tether Mad1-Mad2 at kinetochores and sustain SAC arrest in cells challenged with spindle poisons. We also show that RZZ forms the mesh-like fibrous corona, a structural expansion of the outer kinetochore important for timely chromosome congression [10-13] once Mps1 phosphorylates the N-terminus of Rod. Artificially tethering Mad1-Mad2 to kinetochores enabled long-term mitotic arrest in the absence of RZZ. Conversely, blocking early RZZ-independent recruitment of Mad1-Mad2 eliminated the transient SAC response in RZZ-null cells. We conclude that RZZ drives structural changes in the outer kinetochore that facilitate chromosome biorientation and chronic SAC transduction, a key determinant of cytotoxicity during antimitotic drug therapy [14-16]. All rights reserved. No reuse allowed without permission. Results Recent studies have reached different conclusions about the specific roles and relative importance of Bub1 and the RZZ complex in targeting Mad1-Mad2 to kinetochores and transducing SAC arrest [4] [5] [6] [7] [8] . To interrogate RZZ function with maximum penetrance, we used AAV (adeno-associated virus)-and CRISPR-mediated gene editing to target the KNTC1 (Rod) locus in HCT116 cells, a diploid colorectal cell line ( Fig. S1A-C) . The resulting KNTC1 HF/-(hypomorph-flox) cells expressed Rod at ~20% of the wildtype level ( Fig. 1A -B and S1D) and exited mitosis prematurely when microtubule polymerization (nocodazole, 99 ± 6 min s.e.m.) or Eg5-dependent spindle bipolarity (S-trityl-L-cysteine (STLC), 193 ± 9 min s.e.m.) were inhibited, whereas wildtype cells never exited mitosis during the 16-hour timelapse (Fig. 1A-B) . To determine if complete loss of the RZZ complex is compatible with clonogenic survival, KNTC1 HF/cells were transduced with an adenovirus expressing Cre recombinase (AdCre) and subjected to limiting dilution.
Output: The RZZ complex integrates spindle checkpoint maintenance with dynamic expansion of unattached kinetochores
Background: Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (R E ) in the context of the 2010 measles epidemic in Malawi. Methods: Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, R E , at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. Results: The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated R E ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. Conclusions: Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.
Output: Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi
Monoclonal antibodies to the Quebec isolate of bovine coronavirus were produced and characterized . Monoclonal antibodies to both the E2 and the E3 glycoproteins were found to efficiently neutralize virus in vitro. None of the monoclonal antibodies directed against the El glycoprotein neutralized virus infectivity . Neutralizing monoclonal antibodies to the E2 glycoprotein were all found to immunoprecipitate gpl 90, gpl 00, and their intracellular precursor protein gp170. Neutralizing monoclonal antibodies to the E3 glycoprotein immunoprecipitated gp124 and showed differential reactivity to its precursor proteins gp59 and gpl 18 . These monoclonal antibodies also showed differential reactivity to an apparent degradation product of E3 . Neutralizing monoclonal antibodies to E2 bound to two distinct nonoverlappig antigenic domains as defined by competitive binding assays . Neutralizing monoclonal antibodies to the E3 glycoprotein also bound to two distinct antigenic sites as defined by competitive binding assays plus a third site which overlapped these regions . Other results indicated that one domain on the E3 glycoprotein could be further subdivided into two epitopes . Thus four epitopes could be defined by E3-specific monoclonal antibodies . C 1987 Academic Press, Inc .
Output: Monoclonal Antibodies to Bovine Coronavirus : Characteristics and Topographical Mapping of Neutralizing Epitopes on the E2 and E3 Glycoproteins'
Background: Changes in the levels of circulating microRNAs (miRNAs) in the serum of humans and animals have been detected as a result of infection with a variety of viruses. However, to date, such a miRNA profiling study has not been conducted for foot-and-mouth disease virus (FMDV) infection. The relative abundance of 169 miRNAs was measured in bovine serum collected at three different phases of FMDV infection in a proof-of-concept study using miRNA PCR array plates. Results: Alterations in specific miRNA levels were detected in serum during acute, persistent, and convalescent phases of FMDV infection. Subclinical FMDV persistence produced a circulating miRNA profile distinct from cattle that had cleared infection. bta-miR-17-5p was highest expressed during acute infection, whereas bta-miR-31 was the highest during FMDV persistence. Interestingly, miR-1281was significantly down-regulated during both acute and persistent infection. Cattle that cleared infection resembled the baseline profile, adding support to applying serum miRNA profiling for identification of sub-clinically infected FMDV carriers. Significantly regulated miRNAs during acute or persistent infection were associated with cellular proliferation, apoptosis, modulation of the immune response, and lipid metabolism. Conclusions: These findings suggest a role for non-coding regulatory RNAs in FMDV infection of cattle. Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication, determine if this miRNA signature is applicable across all FMDV serotypes, and may facilitate development of novel diagnostic applications.
Output: Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection
Multicellular organisms are similar to biological communities, consisting of various cell types; thus, inter-cell communication is critical for the functioning of the whole system that ultimately constitutes a living being. Conventional models of cellular exchange include signaling molecules and direct contact-mediated cell communications. Exosomes, small vesicles originating from an inward budding of the plasma membrane, represent a new avenue for signaling between cells. This interchange is achieved by packaging RNA species into exosomes endowed with specific cell surface-targeting motifs. The delivered RNA molecules are functional and mRNA can be translated into new proteins, while miRNAs target host mRNAs in the recipient cell. RNA involved in transmitting information or molecules between cells is called exosomal RNA (esRNA). This review summarizes the characteristics of exosomes, specifically focusing on their role in the horizontal transfer of cellular information. Cell-cell communication; exosomes; esRNA; miRNA Exosomes, originally discovered in reticulocytes 1 , are multivesicular vacuoles and carriers of cellular cargo. Exosomes are the extracellular counterparts of endosomes, which are found in the cytoplasm. Endosomes were discovered in electron microscopic studies 2 and range from 30-80 nM in diameter. They are formed from an inward budding of the plasma membrane, often containing vesicles inside the lumen. To clarify the terminology, 'exosomes' can also refer to multisubunit protein complexes involved in RNA degradation 3 , however, the exosome complexes discussed in this article refer to microvesicular exosomes 4 . Exosomes differ from 'microparticles' released by cells, which arise from a budding of the outer layers of the plasma membrane. Microparticles are much larger than exosomes and range in size from 100 nm to 1 µm in diameter. Exosomes, on the other hand, are formed from endosomes, which in turn arise from an inward budding of the plasma membrane into the cytoplasm. There are often target cell-specific receptor molecules to guide exosomes to their cell of influence. Fusion of the exosomes with the plasma membrane of the recipient cell allows for transfer of the internal components to the target cell and thus, the transfer of information. The molecules being transferred can include proteins such as receptors or enzymes and nucleic acid molecules such as RNA. The RNA included in exosomes is known as exosomal RNA (esRNA). The ability to influence gene expression in distant cells through exosomes presents a remarkable model for cell-to-cell signaling. The horizontal transfer of exosomal RNA offers a new perspective on intercellular
Output: Horizontal Transfer of RNAs: Exosomes as mediators of intercellular communication NIH Public Access
Virus recognition and induction of interferon (IFN) are critical components of the innate immune system. The Toll-like receptor (TLR) and RIG-I-like receptor families have been characterized as key players in RNA virus detection. Signaling cascades initiated by these receptors are crucial for establishment of an IFN signaling mediated antiviral state in infected and neighboring cells and containment of virus replication as well as initiation of the adaptive immune response. In this review, we focus on the diverse and overlapping functions of these receptors, their physiological importance, and respective viral inducers. We highlight the roles of TRL3, TLR7/8, retinoic acid inducible gene I, melanoma differentiation-associated gene 5, and the RNA molecules responsible for activating these viral sensors.
Output: Induction of type I interferon by RNA viruses: cellular receptors and their substrates
The impact of COVID-19 pandemic on the global health and world's economy have been profound and unseen since the Spanish flu of 1918-19. As of now, many countries have been severely affected, partly because of slow responses to the crisis, ill-preparedness of their health system, and the fragile health infrastructure and the shortage of protective equipment. This note evaluates various scenarios, based on an estimation of number of identified and unidentified infected cases, and examines the effectiveness of different policy responses to contain this pandemic. Our result, based on an estimation of the model for Iran, show that in many instances the number of unidentified cases, including asymptomatic individuals, could be much bigger than the reported numbers. The results confirm that in such circumstances, social distancing alone cannot be an effective policy unless a large portion of the population confine themselves for an extended period of time, which is not only difficult to implement, but it could also prove extremely costly and damaging to the economy. An alternative policy, this note argues, is to couple effective social distancing with extensive testing, even to those who are asymptomatic, and isolate the identified cases actively. Otherwise, many lives will be lost, and the health system will collapse, adding to the ongoing economic troubles that many countries have started to encounter. JEL classification: I10, I18, I19.
Output: Modeling of COVID-19 Pandemic and Scenarios for Containment *
Infectious bronchitis (IB) is one of the most important viral diseases of poultry. The aim of this study was to investigate the distribution of avian infectious bronchitis virus isolate IRFIBV32 (793/B serotype) in experimentally infected chicken. Ninetyone-day-old commercial broilers were divided randomly into two groups (seventy in the experimental and twenty in the control group). Chicks in the experimental group were inoculated intranasally with 10 5 ELD50/0.1 mL of the virus at three weeks of age. The samples from various tissues were collected at1, 2, 3, 5, 7, 11, 13, 15, and 20 days postinoculation. Chickens exhibited mild respiratory signs and depression. Viral RNA was detected in the kidney, lung and tracheas on days 1 to 13 PI, in the oviduct between, days 3 and 13, in testes between days 1 and 11 PI, and in the caecal tonsil consistently up to day 20 PI. The most remarkable clinical signs and virus detection appeared on day 1 PI. Data indicated that the number of infected chickens and viral RNA detection from tissues was reduced with increasing antibody titer on day 20 PI. The results demonstrated that the IRFIBV32 virus has wide tissue distribution for respiratory, urogenital, and digestive systems.
Output: Pathogenesis and Tissue Distribution of Avian Infectious Bronchitis Virus Isolate IRFIBV32 (793/B Serotype) in Experimentally Infected Broiler Chickens
The unclassified bovine enteric calicivirus (BEC) is a new bovine enteric calicivirus that is different from bovine norovirus, and causes diarrhea and pathologies in the small intestine of calves. This virus includes Nebraska (NB)-and Newbury agent 1 (NA1)-like strains. The prevalence of this BEC and its genetic characterization has only been reported in the UK and the USA. This study examined the prevalence and genetic diversity of these BECs in diarrheic calves in South Korea. Among a total of 645 diarrheic fecal specimens obtained from 629 cattle herds, these unclassified BECs were detected in 59 (9.1%) diarrheic fecal samples from 57 herds (9.3%) by either RT-PCR or nested PCR. Sequence and phylogenetic analyses of the partial RdRp gene showed that all the Korean BECs clustered together and were closely related to the NB-like viruses (80.9-88.1% nucleotide and 84.5-98.4% amino acid) but not to the NA1-like viruses (75.8-78.4% nucleotide and 79.7-82.8% amino acid). Although these viruses could not be classified into NA1-and NB-like viruses from the sequence and phylogenetic data of the entire capsid gene, all the Korean BECs clustered together on a branch separate from the other known BECs. These results show that these BEC infections are endemic in diarrheic calves in South Korea. The infecting strains are genetically closer to the NB-like viruses but have a distinct evolutionary pathway. #
Output: Molecular detection and characterization of unclassified bovine enteric caliciviruses in South Korea
The aim of this study was to evaluate the image quality of ultra-low-dose computed tomography (ULDCT) and its diagnostic performance in making a specific diagnosis of pneumonia in febrile neutropenic patients with hematological malignancy. ULDCT was performed prospectively in 207 febrile neutropenic patients with hematological malignancy. Three observers independently recorded the presence of lung parenchymal abnormality, and also indicated the cause of the lung parenchymal abnormality between infectious and noninfectious causes. If infectious pneumonia was considered the cause of lung abnormalities, they noted the two most appropriate diagnoses among four infectious conditions, including fungal, bacterial, viral, and Pneumocystis pneumonia. Sensitivity for correct diagnoses and receiver operating characteristic (ROC) curve analysis for evaluation of diagnostic accuracy were calculated. Interobserver agreements were determined using intraclass correlation coefficient. Of 207 patients, 139 (67%) had pneumonia, 12 had noninfectious lung disease, and 56 had no remarkable chest computed tomography (CT) (20 with extrathoracic fever focus and 36 with no specific disease). Mean radiation expose dose of ULDCT was 0.60±0.15 mSv. Each observer regarded low-dose CT scans as unacceptable in only four (1.9%), one (0.5%), and three (1.5%) cases of ULDCTs. Sensitivity and area under the ROC curve in making a specific pneumonia diagnosis were 63.0%, 0.65 for reader 1; 63.0%, 0.61 for reader 2; and 65.0%, 0.62 for reader 3; respectively. Conclusion ULDCT, with a sub-mSv radiation dose and acceptable image quality, provides ready and reasonably acceptable diagnostic information for pulmonary infection in febrile neutropenic patients with hematologic malignancy.
Output: Ultra-Low-Dose Chest CT in Patients with Neutropenic Fever and Hematologic Malignancy: Image Quality and Its Diagnostic Performance
The binding between peptide epitopes and major histocompatibility complex proteins (MHCs) is an important event in the cellular immune response. Accurate prediction of the binding between short peptides and the MHC molecules has long been a principal challenge for immunoinformatics. Recently, the modeling of MHC-peptide binding has come to emphasize quantitative predictions: instead of categorizing peptides as "binders" or "non-binders" or as "strong binders" and "weak binders", recent methods seek to make predictions about precise binding affinities. We developed a quantitative support vector machine regression (SVR) approach, called SVRMHC, to model peptide-MHC binding affinities. As a non-linear method, SVRMHC was able to generate models that out-performed existing linear models, such as the "additive method". By adopting a new "11-factor encoding" scheme, SVRMHC takes into account similarities in the physicochemical properties of the amino acids constituting the input peptides. When applied to MHC-peptide binding data for three mouse class I MHC alleles, the SVRMHC models produced more accurate predictions than those produced previously. Furthermore, comparisons based on Receiver Operating Characteristic (ROC) analysis indicated that SVRMHC was able to outperform several prominent methods in identifying strongly binding peptides. As a method with demonstrated performance in the quantitative modeling of MHCpeptide binding and in identifying strong binders, SVRMHC is a promising immunoinformatics tool with not inconsiderable future potential.
Output: Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models
Adult T-cell leukemia/lymphoma is a distinct clinical entity characterized by a clonal proliferation of malignant T-lymphocytes. The etiologic agent of the disease is a Human T-cell lymphotropic virus type I. It occurs almost exclusively in areas where the virus is endemic; however the disease develops only in the minority of patients who are virus carriers. Karyotyping findings and their correlation with clinical features are still limited in T-cell malignancies, complicated by clinical heterogeneity and a plethora of secondary abnormalities. This study describes detailed chromosomal and fluorescence in situ hybridization results observed in a patient with adult T-cell leukemia/lymphoma and correlates them with clinical characteristics.
Output: Genomic instability and rapid clinical course in adult T-cell lymphoma/leukemia patient