niryuu/sni-each-converted huggingface dataset:
Highlights d N 1 -2 0 O-methylation is crucial to block RIG-I activation by viral and self RNA d Self-RNA exclusion is singularly governed by the conserved H830 in RIG-I d H830A alteration leads to indiscriminate recognition of endogenous RNA by RIG-I d Cellular N 1 -2 0 O-methyltransferase knockdown renders endogenous RNA stimulatory SUMMARY The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5 0 -triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5 0 -triphosphorylated, backbone modifications and the 5 0 -ppp-linked methylguanosine ( m7 G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5 0 -terminal nucleotide (N 1 ) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N 1 -2 0 O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N 1 -2 0 O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N 1 -2 0 O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2 0 O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N 1 -2 0 O-methylation in RIG-I tolerance of self-RNA. 42 Immunity 43, 41-51, July 21, 2015 ª2015 Elsevier Inc.
Output: A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N 1 -2 0 O-Methylated Self RNA Article A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N 1 -2 0 O-Methylated Self RNA
Background: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). Methods: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012-2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60-79% moderate performance; ≥80% good performance. Results: During 2012-2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December-May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. Conclusions: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.
Output: Evaluation of the influenza sentinel surveillance system in the Democratic Republic of Congo, 2012-2015
An infectious disease that is transmitted from animals to humans, sometimes by a vector, is called zoonosis. The focus of this review article is on the most common emerging and re-emerging bacterial zoonotic diseases. The role of "One Health" approach, public health education, and some measures that can be taken to prevent zoonotic bacterial infections are discussed. • A zoonotic bacterial disease is a disease that can be very commonly transmitted between animals and humans. Global climate changes, overuse of antimicrobials in medicine, more intensified farm settings, and closer interactions with animals facilitate emergence or re-emergence of bacterial zoonotic infections. • The global "One Health" approach, which requires interdisciplinary collaborations and communications in all aspects of health care for humans, animals, and the environment, will support public health in general. • New strategies for continuous dissemination of multidisciplinary research findings related to zoonotic bacterial diseases are hence needed.
Output: PUBLIC HEALTH REVIEW ARTICLE
are key components of the ubiquitinproteasome-system (UPS). The fundamental role of DUBs is specific removal of ubiquitin from substrates. DUBs contribute to activation/deactivation, recycling and localization of numerous regulatory-proteins, thus playing major roles in diverse cellular-processes. Altered DUB activity is associated with multitudes of pathologies including cancer. Therefore, DUBs represent novel candidates for target-directed drug development. Areas covered-The article is a thorough review/accounting of patented compounds targeting DUBs stratifying/classifying the patented compounds based on: chemical-structures, nucleic-acid compositions, modes-of-action and targeting-sites. The review provides a brief background on the UPS and DUBs involvement. Furthermore, methods for assessing efficacy and potential pharmacological utility of DUB inhibitor (DUBi) are discussed. Expert opinion-The FDA's approval of the 20S proteasome inhibitors: bortezomib and carfilzomib for treatment of hematological malignancies established the UPS as an anti-cancer target. Unfortunately, many patients are inherently resistant or develop resistance to proteasome inhibitors (PIs). One potential strategy to combat PI resistance is targeting upstream components of the UPS such as DUBs. DUBs represent a promising potential therapeutic target due to their critical roles in various cellular processes including protein-turnover, localization and cellular homeostasis. While considerable efforts have been undertaken to develop DUB modulators, significant advancement is necessary move DUB inhibitors into the clinic.
Output: Deubiquitinases (DUBs) and DUB inhibitors: a patent review HHS Public Access
To determine the role of biomarkers in the clinical management of respiratory complications (RC) in hematopoietic stem cell transplantation (HSCT) recipients, we have prospectively evaluated a cohort of 175 patients followed-up for 1 year after HSCT. To avoid misinterpretation, we have excluded both unidentified respiratory infections (RI) and mixed RI. A total of 64 RC were included. Plasma levels of C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) were measured at diagnosis and on day 3 and 7. Different cytokines were evaluated in serum on the first day. No HSCT recipients without RC were included as a control group. Compared with RI, non-infectious RC showed a significant increase in CRP, proADM and interleukin 6 on day 0 (P = 0.005; P = 0.03 and P = 0.04, respectively). When only RI were considered, we observed that bacterial-fungal PI showed higher levels of CRP (P = 0.02), PCT (P = 0.04) and proADM (P o0.01). Persistent low levels of proADM biomarkers suggest viral infection (specificity and positive predictive value 100%). Patients dying of RC had PCT and proADM levels higher than survivors (P = 0.002 and P = 0.03, respectively). In HSCT recipients biomarkers increase in both infectious and non-infectious RC. They may have utility in the assessment of the severity of RC and in suspecting a viral etiology.
Output: The clinical value of biomarkers in respiratory complications in hematopoietic SCT
The acute phase of respiratory distress caused by porcine reproductive and respiratory syndrome virus (PRRSV) is likely a consequence of the release of inflammatory cytokines in the lung. IL-8, the main chemokine and activator of neutrophils, might be related to the lung injury upon PRRSV infection. In this study, we showed that PRRSV induced IL-8 expression in vivo and in vitro. Subsequently, we demonstrated that JNK and NF-κB pathways were activated upon PRRSV infection and required for the enhancement of IL-8 expression. We further verified that PRRSV-activated TAK-1 was essential for the activation of JNK and NF-κB pathways and IL-8 expression. Moreover, we revealed an AP-1 binding motif in the cloned porcine IL-8 (pIL-8) promoter, and deletion of this motif abolished the pIL-8 promoter activity. Finally, we found that the JNK-activated AP-1 subunit c-Jun was critical for the up-regulation of IL-8 expression by PRRSV. These data suggest that PRRSVinduced IL-8 production is likely through the TAK-1/JNK/AP-1 pathways. http://dx.
Output: Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways
For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes.
Output: BIOLOGYjMEDICINE Viruses and viral proteins
Background: Febrile seizures are common in young children. Annual peaks in incidence mirror increased respiratory virus activity during winter. Limited virological data are available using modern diagnostic techniques for children with febrile seizures. We aimed to determine the frequency of detection of specific viral pathogens in children with febrile seizures, to describe risk factors including recent vaccination and clinical features associated with specific etiologies. Methods: An observational study was performed. Children aged 6 months to 5 years presenting to the Emergency Department of a tertiary children's hospital in Western Australia with febrile seizures were enrolled between March 2012 and October 2013. Demographic, clinical data and vaccination history were collected, and virological testing was performed on per-nasal and per-rectal samples. Results: One hundred fifty one patients (72 female; median age 1.7y; range 6 m-4y9m) were enrolled. Virological testing was completed for 143/151 (95%). At least one virus was detected in 102/143 patients (71%). The most commonly identified were rhinoviruses (31/143, 22%), adenovirus (30/151, 21%), enteroviruses, (28/143, 20%), influenza (19/143, 13%) and HHV6 (17/143, 12%). More than one virus was found in 48/143 (34%). No significant clinical differences were observed when children with a pathogen identified were compared with those with no pathogen detected. Febrile seizures occurred within 14 days of vaccine administration in 16/151 (11%). Conclusion: At least one virus was detected in over two thirds of cases tested (commonly picornaviruses, adenovirus and influenza). Viral co-infections were frequently identified. Febrile seizures occurred infrequently following immunization.
Output: An observational study of febrile seizures: the importance of viral infection and immunization
The importance of host transmissibility in disease emergence has been demonstrated in historical and recent pandemics that involve infectious individuals, known as superspreaders, who are capable of transmitting the infection to a large number of susceptible individuals. To investigate the impact of superspreaders on epidemic dynamics, we formulate deterministic and stochastic models that incorporate differences in superspreaders versus nonsuperspreaders. In particular, continuous-time Markov chain models are used to investigate epidemic features associated with the presence of superspreaders in a population. We parameterize the models for two case studies, Middle East respiratory syndrome (MERS) and Ebola. Through mathematical analysis and numerical simulations, we find that the probability of outbreaks increases and time to outbreaks decreases as the prevalence of superspreaders increases in the population. In particular, as disease outbreaks C. J. Edholm ( )
Output: Searching for Superspreaders: Identifying Epidemic Patterns Associated with Superspreading Events in Stochastic Models
The outpost position of the olfactory bulb (OB) between the direct inputs from sensory neurons of the nasal epithelium and other parts of the brain suggests its highest vulnerability among all brain structures to penetration of exogenous agents. A number of neurotropic viruses have been found to invade the brain through the OB. There is growing evidence that microscopic particles of toxic dusts can propagate from the nasal epithelium to the OB and further into the brain. These harmful agents impair cellular elements of the brain. Apparently, cells in the OB are the most affected, as they are the first to encounter viral infections and toxic particles. It is well known that neuronal and glial progenitors are continuously generated from neuronal stem cells in the subventricular zone of the adult brain and then migrate predominantly into the OB. Therefore, it is feasible to suggest that substitution of injured or dead cells in the OB by new-born neurons, differentiating from progenitors, plays a role in protecting the OB neuronal microcircuits from destruction. Furthermore, some cytokines and chemokines released in response to infection and/or intoxication can modulate different stages of neurogenesis (proliferation, migration, and differentiation). We hypothesize that continuous neurogenesis in the olfactory system throughout adulthood evolved as a protective mechanism to prevent impairment of the most ancient but vitally important sensory system. In addition, differentiation of a substantial portion of progenitors to glial cells, including macrophages and microglia, may create an additional barrier to exogenous agents on their way deep to the brain.
Output: Neurogliogenesis in the mature olfactory system: A possible protective role against infection and toxic dust
We conducted a cross-sectional study of risk factors for herd-level kid positivity for Cryptosporidium parvum oocysts in dairy-goat farms (Deux-Sèvres, western France). From January to March 2003, faeces from a convenient sample of 879 5-to 30-day-old goat kids from 60 herds were examined microscopically after staining with carbol fuschin. Oocyst shedding was scored semi-quantitatively (0 to 4+) allowing us to obtain a cumulative score per herd. Standardized questionnaires with information about management practices were collected in each farm. We found positive kids in 32 of 60 herds (53.3%) and in 142 animals out of 879 (16.2%). We used logistic regression for two risk-factor model: (1) simple positive (case: herd score !1+, at least one positive kid in the herd, versus control: herd score = 0), (2) strongly positive (case: overall herd score !3+ versus control: herd score <3+). Risk factors associated with simple positive herds were period of sampling compared to the peak of births (After versus Before, OR = 4.2, 95% CI 1.2, 15.3) and practice of kid grouping by age or weight (Yes versus No, OR = 4.4, 95% CI 1.0, 19.1). Risk factors associated with strongly positive herds were period of investigation (February/March versus January, OR = 12.7, 95% CI 2.1, 76.6), exposure to graminaceous plants in forage (OR = 11.6, 95% CI 1.7, 81.0) and type of ventilation in the goat premises (Vertical versus Wind effect, OR = 14.7, 95% CI 2.1, 106.1). No important association was found between www.elsevier.com/locate/prevetmed Preventive Veterinary Medicine 77 (2006) 109-121 kid-management practices and herd positivity. These results suggest a major role of the environment of kids during their first hours of life in the adult-goat premises regarding the transmission of C. parvum infection.
Output: Herd-level risk factors for Cryptosporidium infection in dairy-goat kids in western France
Infectious diseases represent a continuous and increasing threat to human health and welfare. Due to emerging diseases, increasing resistances, international travelling, and the risk of bioterroristic attacks, infectious diseases concern the whole world and can only be combated by internationally coordinated and interdisciplinary approaches. When assessing the worldwide publication activities on infectious diseases in the years 1994-2004 accessible via the ISI Science Citation Index Expanded s , an overall increase by 24% can be monitored. Furthermore, it becomes evident that highest research priorities are given to HIV/AIDS, hepatitis C, tuberculosis, respiratory infections, and sepsis. Ten countries -including the USA, the UK, France, Germany, and Japan -contributed to more than 80% of these publications; nation-specific research priorities focusing on the current problems in the respective country can be estimated. Countries with the highest disease burdens are still not given the opportunity to contribute adequately to the scientific field. Based on our data, relatively increasing publication activities include those on respiratory infections, tuberculosis, malaria, hepatitis, and sepsis, whereas decreasing activities were determined for AIDS, diarrhoea, meningitis, schistosomiasis, and other diseases. Accordingly, the prevalence of many infectious diseases occurring in tropical countries is not clearly reflected in the worldwide publication activities.
Output: Infectious diseases -A global challenge
Objective: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animalborne emerging infectious disease. Design: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. Setting: Models were applied to estimate the overall burden of H7N9 cases in China. The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.
Output: Calculating the burden of disease of avian-origin H7N9 infections in China
Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3-4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3-5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA + β7 + (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets.
Output: Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets
A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD + )-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADPribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases. OPEN ACCESS Cells 2015, 4 570
Output: Intracellular Mono-ADP-Ribosylation in Signaling and Disease
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. A n n P a t h o l 2 0 0 5 ; 2 5 : 3 4 9 -5 6 © M a s s o n , P a r i s , 2 0 0 5 349 Article original Accepté pour publication le 25 août 2005 Tirés à part : P. Hofman, voir adresse en début d'article.
Output: Diagnostic histologique des infections bactériennes nécrosantes extensives du poumon Étude de 4 observations d'évolution fulminante
Neonatal calf diarrhoea triggered by the enteric protozoan parasite Cryptosporidium is a leading cause of morbidity and mortality in calves aged 1-month-old or younger globally. Infected cattle in general and calves in particular have also been demonstrated as major contributors of zoonotic C. parvum oocysts in the environment and have been linked to a number of waterborne outbreaks of human cryptosporidiosis. Little is known on the occurrence, geographical distribution, and molecular diversity of Cryptosporidium infections affecting bovine populations in Algeria. In this study faecal specimens were randomly collected from 460 cattle aged between two days and 18 months on 10 farms located in the provinces of Aïn Defla, Blida, Sétif, and Tizi Ouzou between the autumn of 2015 and the spring of 2016. Faecal samples were microscopically examined using the modified Ziehl-Neelsen acid-fast technique as screening method. Microscopy-positive samples were confirmed by a commercial coproantigen enzyme-linked immunosorbent assay (Bio-X Diagnostics). The identification of Cryptosporidium species and sub-genotypes in confirmed samples was conducted by PCR and sequence analyses of the small subunit ribosomal RNA (ssu rRNA) and the 60 kDa glycoprotein (gp60) genes of the parasite. Overall, 52.2% (240/460) of the investigated cattle tested positive to Cryptosporidium by microscopy. The infection was widespread in all 10 farms surveyed, but was significantly more prevalent in those from Blida in the central part of the country. Bovine cryptosporidiosis affected cattle of all age groups but with different outcomes. Pre-weaned (up to one month old) calves typically presented with diarrhoea, whereas older animals mostly harboured subclinical infections. The commercial ELISA used only detected 15.8% (38/240) of the samples that previously tested positive by microscopy, demonstrating a poor performance in field epidemiological surveys. Sequence analysis of the 29 isolates generated at the ssu rRNA loci confirmed the presence of four Cryptosporidium species including C. parvum (72.4%), C. bovis (13.8%), C. andersoni, (3.4%), and C. ryanae (3.4%). Two additional isolates (7.0%) could only be identified at the genus level. Eight out of the 21 isolates assigned to C. parvum were identified as sub-genotype IIaA16G2R1 at the gp60 locus. C. parvum was almost exclusively found infecting preweaned calves, whereas C. ryanae and C. andersoni were only detected in asymptomatic animals. Bovine cryptosporidiosis is highly endemic in the surveyed area and represents a veterinary public health concern that should be adequately tackled by Algerian veterinary health authorities and policy makers.
Output: Cryptosporidium-associated diarrhoea in neonatal calves in Algeria
a summary of the evolution of infectiousness over time. When who-infects-whom is observed, the Nelson-Aalen estimator produces an unbiased estimate of the cumulative hazard function of the contact interval distribution. When who-infects-whom is not observed, we use an EM algorithm to average the Nelson-Aalen estimates from all possible combinations of who-infected-whom consistent with the observed data. This converges to a nonparametric maximum likelihood estimate of the cumulative hazard function that we call the marginal Nelson-Aalen estimate. We study the behavior of these methods in simulations and use them to analyze household surveillance data from the 2009 influenza A(H1N1) pandemic.
Output: Nonparametric survival analysis of infectious disease data Summary
A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC 50 (50% effective concentration) = 27.6-91.5 µM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK − ) VZV strain (EC 50 = 27.59 µM), while 16d was the most potent towards TK + VZV (EC 50 = 29.91 µM). Cytostatic properties of the compounds 14a-i-17a-i were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC 50 (50% inhibitory concentration) = 29-130 µM] and L1210 cells [IC 50 (50% inhibitory concentration) = 14-142 µM].
Output: Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates
Transmissible gastroenteritis coronavirus (TGEV) is enteropathogenic coronavirus that causes diarrhea in pigs, and is associated with high morbidity and mortality in sucking piglets. The TGEV membrane (M) protein is a decisive protein for the proliferation of viral proteins, and is associated with virus assembly and budding. To identify the cellular proteins that interact with the TGEV M protein, yeast two-hybrid screening was employed, and seven cellular proteins were identified M-binding partners. Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. Additionally, confocal microscopy revealed that EIF4A2 and M were colocalized in the cytoplasm. Furthermore, the function of EIF4A2 in intestinal cells during TGEV infection was examined. A knockdown of EIF4A2 by siRNA markedly decreased M protein proliferation and TGEV replication in target cells. Thus demonstrating that EIF4A2 plays a significant role in TGEV replication. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection.
Output: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication
Background: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. Results: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. Conclusions: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation.
Output: 8S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells
Background: The cynomolgus monkey (Macaca fascicularis) has been increasingly used as a non-human primate model in biomedical research. As establishing baseline thoracic radiography for the cynomolgus monkey is essential, we tested the hypothesis that age and sex may affect the thoracic radiography parameters of this species. Methods: Here, 697 healthy cynomolgus monkeys were segregated by sex and age (three age groups: 25-36 months, 37-48 months, 49-60 months). The lung length (LL), maximal interior thoracic depth (TD), maximal interior thoracic breadth (TBr), cardiac silhouette breadth (CBr), cardiothoracic ratio (CR), right and left costophrenic angles (RCA and LCA), and right hilar height ratio (R-HHR) were assessed by chest film. Statistical analysis was applied to examine the effect of age, sex, and age 6 sex interactions. Results: Significant effects by age were shown for LL, TD, TBr, CBr, and CR. Significant effects by sex were found for TD, TBr, CBr, CR, and R-HHR. Significant effects by age 6sex were observed for TD, TBr, CBr, and CR. Both TD and TBr increased with age in both sexes, and both were significantly higher in males than in females in the group aged 49-60 months. CBr increased with age and was significantly higher in males than in females across all age groups. CR declined with age and was significantly higher in males than females across all age groups, and CR was similar or slightly higher relative to those previously found in other non-human primate species. As to the other parameters with no significant sex nor age-related differences, the R-HHR was greater than 1.00, and the angulation of bilateral costophrenic angles were sharp. The thoracic radiographic parameters for the healthy cynomolgus monkey presented here should prove useful in veterinary practice, research involving non-human primate models of respiratory or cardiovascular disorders, and morphological studies on cynomolgus monkeys.
Output: Normal Thoracic Radiographic Appearance of the Cynomolgus Monkey (Macaca fascicularis)
This chapter provides an overview of the global use of herpetofauna in traditional folk medicine and the implications for conservation. The results indicate that 331 species (284 reptiles and 47 amphibians) are used in traditional folk medicine around the world. Among the species recorded, 182 reptiles and 42 amphibians are listed in the IUCN Red List. Additionally, 93 reptiles are in some of the appendices of CITES. These numbers demonstrate the importance of understanding such medicinal uses in the context of reptile conservation as well as the need for considering sociocultural factors when establishing management plans directed toward the sustainable use of these reptiles.
Output: Herpetofauna Used in Traditional Folk Medicine: Conservation Implications
OBJECTIVE-To estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women. METHODS-In a prospective cohort study of HIV-1-infected women and their infants, mode of delivery was determined by clinicians at the participating sites. For this analysis, "elective cesarean delivery" was defined as any cesarean delivery, regardless of gestational age, without labor and with duration of ruptured membranes of less than 5 minutes. Nonelective cesarean deliveries were those performed after the onset of labor, rupture of membranes, or both. Vaginal delivery included normal spontaneous and instrument deliveries. Associations between mode of delivery and infant respiratory morbidity were assessed using χ 2 or Fisher's exact test. Adjusted odds of respiratory distress syndrome by delivery mode were assessed using multivariable logistic regression. RESULTS-Among 1,194 mother-infant pairs, there were significant differences according to mode of delivery in median gestational age (weeks) at delivery (vaginal, n=566, median=38.8; nonelective cesarean, n=216, median=38.0; and elective cesarean, n=412, median 38.1; P<.001) and incidence of respiratory distress syndrome (vaginal, n=9, 1.6%, reference; nonelective cesarean, n=16, 7.4%; elective cesarean, n=18; 4.4%; (P<.001). In analyses adjusted for gestational age and birth weight, mode of delivery was not statistically significantly associated
Output: Mode of Delivery and Infant Respiratory Morbidity Among Infants Born to HIV-1-Infected Women NIH Public Access Author Manuscript
This study investigated the performance of various case definitions and influenza symptoms in a primary healthcare sentinel surveillance system. A retrospective study of the clinical and epidemiological characteristics of the cases reported by a primary healthcare sentinel surveillance network for eleven years in Catalonia was conducted. Crude and adjusted diagnostic odds ratios (aDORs) and 95% confidence intervals (CIs) of the case definitions and symptoms for all weeks and epidemic weeks were estimated. The most predictive case definition for laboratory-confirmed influenza was the World Health Organization (WHO) case definition for ILI in all weeks (aDOR 2.69; 95% CI 2.42-2.99) and epidemic weeks (aDOR 2.20; 95% CI 1.90-2.54). The symptoms that were significant positive predictors for confirmed influenza were fever, cough, myalgia, headache, malaise, and sudden onset. Fever had the highest aDOR in all weeks (4.03; 95% CI 3.38-4.80) and epidemic weeks (2.78; 95% CI 2.21-3.50). All of the case definitions assessed performed better in patients with comorbidities than in those without. The performance of symptoms varied by age groups, with fever being of high value in older people, and cough being of high value in children. In patients with comorbidities, the performance of fever was the highest (aDOR 5.45; 95% CI 3.43-8.66). No differences in the performance of the case definition or symptoms in influenza cases according to virus type were found.
Output: Usefulness of Clinical Definitions of Influenza for Public Health Surveillance Purposes and on behalf of the PIDIRAC Sentinel Surveillance Program of Catalonia †
Background. Human bocavirus (HBoV) was recently discovered in children with respiratory tract disease and gastroenteritis. The causative role of HBoV in human gastroenteritis remains uncertain, and, to our knowledge, no previous case-control study has studied the relationship between HBoV and gastroenteritis. Methods. We conducted a case-control study that examined stool samples from 397 children with diarrhea and from 115 asymptomatic control subjects. HBoV was detected using polymerase chain reaction. Real-time polymerase chain reaction was used to quantify the HBoV loads in case and control groups. Common enteric viruses were examined using enzyme-linked immunosorbent assays, polymerase chain reaction, and reverse-transcription polymerase chain reaction. Results. At least 1 viral agent was discovered in 60.2% of cases. HBoV was detected in 14 samples, and 9 were coinfected with either rotavirus (7 of 14 samples) or human calicivirus (2 of 14). Many (8 [57.1%] of 14) of the HBoV infections occurred during September-December 2006. Most (12 [85.7%]) of the HBoV-infected children were 7-18 months of age. The percentage of children with HBoV infection did not differ significantly between case patients and control subjects (3.5% vs. 3.5%), and the statistical analysis did not support a correlation between HBoV infection and more-severe clinical symptoms. The viral load differences between the 2 groups were not statistically significant ( , by log-normal Student's t test). In addition, the VP1/VP2 partial gene of HBoV P p .09 from case patients and control subjects showed minimal sequence variation. A single genetic lineage of HBoV was revealed in persons in China. Despite its high prevalence in stool samples, our study does not support a causative role of HBoV in gastroenteritis.
Output: Human Bocavirus in Children Hospitalized for Acute Gastroenteritis: A Case-Control Study
Viral channel forming proteins (VCPs) have been discovered in the late 70s and are found in many viruses to date. Usually they are small and have to assemble to form channels which depolarize the lipid membrane of the host cells. Structural information is just about to emerge for just some of them. Thus, computational methods play a pivotal role in generating plausible structures which can be used in the drug development process. In this review the accumulation of structural data is introduced from a historical perspective. Computational performances and their predictive power are reported guided by biological questions such as the assembly, mechanism of function and drug-protein interaction of VCPs. An outlook of how coarse grained simulations can contribute to yet unexplored issues of these proteins is given. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
Output: Viral channel forming proteins -How to assemble and depolarize lipid membranes in silico ☆
As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill. 2 www.thelancet.com/respiratory Published online April 6, 2020 https://doi.
Output: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations
The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.
Output: Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks
Background. Kawasaki disease (KD) is an acute systemic vasculitis with unknown etiology. The diagnosis of KD depends on clinical manifestations. The prevalence of coronary artery abnormality (CAA) is 11.0% and results in cardiac sequelae, such as myocardial infarction or coronary aneurysm, which are the most serious complications in KD. Methods. We divided KD's children into different age groups: ≤6 months old, 7 months to 1 year old, and >1 year old, respectively. Different parameters were compared in each group. Results. Infants ≤6 months old are less likely to fulfill KD's major diagnostic criteria within 10 days, are prone to develop incomplete KD with the lowest cholesterol level, and have the greatest chance to have CAA and the laboratory features associated with CAA, such as the longest time needed to confirm CA diagnosis, lower hemoglobin level, lower albumin level, and higher platelet count. Infants <1 year old develop higher percentage of leukocytosis and sterile pyuria. But this group has fewer patients with neck lymphadenopathy.
Output: The cientificWorldJOURNAL Research Article Clinical Manifestations Vary with Different Age Spectrums in Infants with Kawasaki Disease
Defining human B cell repertoires to viral pathogens is critical for design of vaccines that induce broadly protective antibodies to infections such as HIV-1 and influenza. Single B cell sorting and cloning of immunoglobulin (Ig) heavy-and light-chain variable regions (V H and V L ) is a powerful technology for defining anti-viral B cell repertoires. However, the Ig-cloning step is time-consuming and prevents high-throughput analysis of the B cell repertoire. Novel linear Ig heavy-and light-chain gene expression cassettes were designed to express Ig V H and V L genes isolated from sorted single B cells as IgG1 antibody without a cloning step. The cassettes contain all essential elements for transcriptional and translational regulation, including CMV promoter, Ig leader sequences, constant region of IgG1 heavy-or Ig light-chain, poly(A) tail and substitutable V H or V L genes. The utility of these Ig gene expression cassettes was established using synthetic V H or V L genes from an anti-HIV-1 gp41 mAb 2F5 as a model system, and validated further using V H and V L genes isolated from cloned EBV-transformed antibody-producing cell lines. Finally, this strategy was successfully used for rapid production of recombinant influenza mAbs from sorted single human plasmablasts after influenza vaccination. These Ig gene expression cassettes constitute a highly efficient strategy for rapid expression of Ig genes for high-throughput screening and analysis without cloning.
Output: Author manuscript; available in PMC
We have characterized the structure, biogenesis, and localization of dipeptidyl aminopeptidase B (DPAP B), a membrane protein of the yeast vacuole. An antibody specific for DPAP B recognizes a 120-kD glycoprotein in yeast that behaves like an integral membrane protein in that it is not removed from membranes by high pH Na2COs treatment. Inspection of the deduced amino acid sequence of DPAP B reveals a hydrophobic domain near the NH2 terminus that could potentially span a lipid bilayer. The in vitro enzymatic activity and apparent molecular weight of DPAP B are unaffected by the allelic state of PEP4, a gene essential for the proteolytic activation of a number of soluble vacuolar hydrolases. DPAP B is synthesized as a glycosylated precursor that is converted to the mature 120-kD species by carbohydrate addition. The precur-J. H. Rothman's present address is
Output: Structure, Biosynthesis, and Localization of Dipeptidyl Aminopeptidase B, an Integral Membrane Glycoprotein of the Yeast Vacuole
As a result of the efforts of the Human Genome Project and the rise in demand for molecular diagnostic assays, the development and optimization of novel hybridization probes have focused on speed, reliability, and accuracy in the identification of nucleic acids. Molecular beacons (MBs) are single-stranded, fluorophore-labeled nucleic acid probes that are capable of generating a fluorescent signal in the presence of target, but are dark in the absence of target. Because of the high specificity and sensitivity characteristics, MBs have been used in variety of fields. In this review, MBs are introduced and discussed as diagnostic tools in four sections: several technologies of MBs will be illustrated primarily; the limitation of MBs next; the third part is new fashions of MBs; and the last one is to present the application of MBs in disease diagnosis.
Output: Molecular Beacons: A Novel Optical Diagnostic Tool