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Sökning: WFRF:(Nordgren Johan)

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1.
  • Aziz, Emad F., et al. (författare)
  • Photoinduced formation of N-2 molecules in ammonium compounds
  • 2007
  • Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 111:39, s. 9662-9669
  • Tidskriftsartikel (refereegranskat)abstract
    • Via fluorescence yield (FY) and resonant inelastic scattering spectroscopy in the soft X-ray range we find that soft X-rays induce formation of N-2 molecules in solid NH4Cl and in related compounds. The nitrogen molecules form weak bonds in NH4Cl, so that a substantial fraction of the molecules remains in the sample. From measurements of the FY as a function of exposure and temperature, the rates for the photochemical processes are estimated. At elevated temperatures (363 K), several nitrogen atoms are removed from the sample per incoming photon. At lower temperatures (233 K), the rate is reduced to around 0.02 nitrogen atoms for each incoming photon. Virtually all these atoms form N-2 molecules which are bound in the sample. The generality and implications of these results are briefly discussed.
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2.
  • Avdic, H. B., et al. (författare)
  • Reduced effects of social feedback on learning in Turner syndrome
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Turner syndrome is a genetic condition caused by a complete or partial loss of one of the X chromosomes. Previous studies indicate that Turner syndrome is associated with challenges in social skills, but the underlying mechanisms remain largely unexplored. A possible mechanism is a reduced social influence on learning. The current study examined the impact of social and non-social feedback on learning in women with Turner syndrome (n=35) and a sex- and age-matched control group (n=37). Participants were instructed to earn points by repeatedly choosing between two stimuli with unequal probabilities of resulting in a reward. Mastering the task therefore required participants to learn through feedback which of the two stimuli was more likely to be rewarded. Data were analyzed using computational modeling and analyses of choice behavior. Social feedback led to a more explorative choice behavior in the control group, resulting in reduced learning compared to non-social feedback. No effects of social feedback on learning were found in Turner syndrome. The current study thus indicates that women with Turner syndrome may be less sensitive to social influences on reinforcement learning, than the general population.
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3.
  • Forsberg, Johan, et al. (författare)
  • Angular anisotropy in resonant inelastic soft X-ray scattering of liquid water
  • 2009
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 79:13, s. 132203-
  • Tidskriftsartikel (refereegranskat)abstract
    • Resonantly excited soft x-ray emission spectra of liquid water have been measured at two different angles relative to the polarization direction of the exciting radiation. The results demonstrate that the emission is much more isotropic than expected for the free water   molecule but that the trends in the remaining anisotropy qualitatively agree. It is found that the two sharp oxygen peaks at high emission energy correspond to states of different symmetry.  
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4.
  • Gråsjö, Johan, et al. (författare)
  • Electronic structure of water molecules confined in a micelle lattice
  • 2009
  • Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 113:24, s. 8201-8205
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxygen K absorption and emission spectra of water molecules confined in dodecyltrimethyl ammonium chloride micelle structures are presented. The local electronic structure of the water molecules is found to be dramatically different from the electronic structure of water molecules in the gas-phase as well as in liquid water. Hybridization with states of the ions in the surrounding ions is directly observed, and evidence for stabilization of the water molecules relative to molecules in bulk water is found.
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7.
  • Agåker, Marcus, et al. (författare)
  • Spectroscopy in the vacuum-ultraviolet
  • 2011
  • Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 5:5, s. 248-248
  • Tidskriftsartikel (refereegranskat)
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8.
  • Akhoondi, Shahab, et al. (författare)
  • FBXW7/hCDC4 is a general tumor suppressor in human cancer
  • 2007
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:19, s. 9006-9012
  • Tidskriftsartikel (refereegranskat)abstract
    • The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skpl-Cdc53/ Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin El, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of ∼ 6%. The highest mutation frequencies were found in tumors of the bile duct (cholangio-carcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational "hotspots," which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.
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9.
  • Andreasson, Eskil, et al. (författare)
  • Integrating Moldflow and Abaqus in the Package Simulation Workflow
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    • Tetra Pak has used numerical simulation tools for plastic injection molding (Moldflow) and structural analysis (Abaqus/Implicit and Abaqus/Explicit) for many years. Today these two simulation tools are used independently of each other without any coupling. How these two disciplines can be combined to better predict the mechanical response of a polymer component is presented in this work. The manufacturing process, in this case injection molding, creates the mechanical properties of the produced polymer part. Process settings, material selection and molding tool geometry affect the polymer flow, material orientation and rate of crystallinity. A method to build a layered finite element model in Abaqus using results from Moldflow simulations regarding crystallinity growth and molecular orientation is proposed. Relatively simple material models were utilized and assigned for each individual material layer through the thickness in the polymer part. These constitutive models were derived phenomenologically from experimental test results and could adequately capture both the microscopic and the macroscopic behavior in a more realistic way. The numerical results showed a good agreement with the experimental results, both regarding visual appearance and force/displacement response.
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11.
  • Barbe, Laure, et al. (författare)
  • Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
  • 2018
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAc beta 3Gal beta 4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
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12.
  • Baroni de Moraes, Marcia Terezinha, et al. (författare)
  • Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection
  • 2019
  • Ingår i: Infection, Genetics and Evolution. - : ELSEVIER SCIENCE BV. - 1567-1348 .- 1567-7257. ; 70, s. 61-66
  • Tidskriftsartikel (refereegranskat)abstract
    • The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b +) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a + b +) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A amp;gt; T, 501C amp;gt; T, 585C amp;gt; T, 855A amp;gt; T and missense substitutions 327C amp;gt; T [S (Ser) amp;gt; C (Cys)], 446 T amp;gt; C [L(Leu) amp;gt; P(Pro)], 723C amp;gt; A [N(Asn) amp;gt; K(Lys)], 724A amp;gt; T [I(Ile) amp;gt; F(Phe)], 736C amp;gt; A [H(His) amp;gt; N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.
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13.
  • Becker-Dreps, Sylvia, et al. (författare)
  • Etiology of Childhood Diarrhea After Rotavirus Vaccine Introduction A Prospective, Population-based Study in Nicaragua
  • 2014
  • Ingår i: The Pediatric Infectious Disease Journal. - : Lippincott, Williams andamp; Wilkins. - 0891-3668 .- 1532-0987. ; 33:11, s. 1156-1163
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. Methods: We followed a population-based sample of children less than5 years in Leon, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. Results: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (less than2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. Conclusions: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.
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15.
  • Bialowas, Sonja, et al. (författare)
  • Intracellularly expressed rotavirus NSP4 stimulates release of serotonin (5-HT) from human enterochromaffin cells
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Rotavirus (RV) is associated with diarrhoea and vomiting, but the mechanisms behind these symptoms remain unresolved. While RV have been shown to infect and stimulate secretion of serotonin (5-hydroxytryptamine; 5-HT) from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice, it remains to identify which intracellularly expressed viral protein (VP) being responsible for this novel property.To address this issue, human EC cells were transfected with small interfering RNA (siRNA) targeting the structural (VP4, VP6 and VP7) and the non-structural protein 4 (NSP4) followed by infection with Rhesus rotavirus (RRV). siRNA specific to NSP4 (siRNANSP4) significantly attenuated secretion of 5-HT compared to siRNAVP4, siRNAVP6 , siRNAVP7 and non-targeting (Nt) siRNAnt. Intracellular calcium clamping with BABTA/AM showed that intracellularly expressed NSP4-stimulated secretion of 5-HT from EC cells was calcium-dependent. Furthermore RV down-regulated the 5-HT transporter (SERT) mRNA in ileum but not tryptophan hydroxylase 1 (TPH1) mRNA the rate-limiting enzyme for 5-HT synthesis. The unaffected expression of TPH1 mRNA in the intestinal segments suggests that release of 5- HT primarily originates from pre-made 5-HT rather than from newly synthesised 5-HT mRNA. Moreover, down-regulation of SERT mRNA in ileum presumably resulted in reduced re- uptake of 5-HT by SERT to EC cells and thus increased extracellular 5-HT in the small intestine. Moreover, 7/7 infant mice responded following intraperitoneal administration of 5-HT with rapid (<30 min) diarrhoea in dose-dependent manner. In the light of these results and the fact that both 5-HT and NSP4 can induce diarrhoea in mice, a disease mechanism to RV diarrhoea is proposed.
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16.
  • Bialowas, Sonja, et al. (författare)
  • Rotavirus and Serotonin Cross-Talk in Diarrhoea
  • 2016
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:7, s. e0159660-
  • Tidskriftsartikel (refereegranskat)abstract
    • Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNA(NSP4)) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNA(VP4), siRNA(VP6) and siRNA(VP7). Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p amp;lt; 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p amp;lt; 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p amp;lt; 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron.
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17.
  • Bjureberg, Johan, et al. (författare)
  • Targeting Maladaptive Anger With Brief Therapist-Supported Internet-Delivered Emotion Regulation Treatments : A Randomized Controlled Trial
  • 2023
  • Ingår i: Journal of Consulting and Clinical Psychology. - : American Psychological Association Press. - 0022-006X .- 1939-2117. ; 91:5, s. 254-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the relative impact of three brief therapist-supported internet-delivered emotion regulation treatments for maladaptive anger (mindful emotion awareness [MEA], cognitive reappraisal [CR], and mindful emotion awareness + cognitive reappraisal [MEA + CR]) and to test whether baseline levels of anger pathology moderate treatment outcome.Method: Treatments were evaluated in a randomized controlled trial. In total, 234 participants (59% female; mean age = 41.1, SD = 11.6) with maladaptive anger were randomized to MEA (n = 78), CR (n = 77), or MEA + CR (n = 79). Self-reported primary and secondary outcomes were followed up at primary endpoint, 3 months after treatment termination (88% retention). Primary outcomes were also assessed weekly during a prolonged baseline phase (4 weeks) and an active treatment phase (4 weeks).Results: At the primary endpoint, the MEA + CR was superior in terms of anger expression (d = 0.27 95% confidence interval, CI [0.03, 0.51]), aggression (d = 0.43 [0.18, 0.68]), and anger rumination (d = 0.41 [0.18, 0.63]). MEA + CR was particularly effective in reducing anger expression (d = 0.66 [0.21, 1.11]), aggression (d = 0.90 [0.42, 1.39]), and anger rumination (d = 0.80 [0.40, 1.20]) for individuals who reported high values (+1SD) of the outcomes at baseline.Conclusions: Brief therapist-supported internet-delivered MEA and CR treatments are effective interventions for maladaptive anger. Combining MEA and CR is especially effective in reducing anger expression and aggression, particularly, in individuals who report higher levels of initial anger pathology. The present study highlights the importance of emotion regulation as an important treatment target for reducing maladaptive anger.
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18.
  • Bonkoungou, Isidore Juste O., et al. (författare)
  • Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction
  • 2018
  • Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 90:9, s. 1453-1460
  • Tidskriftsartikel (refereegranskat)abstract
    • Burkina Faso introduced rotavirus vaccine (RotaTeq) to the national immunization program in November 2013. This study describes the detection rates, clinical profiles, and molecular epidemiology of rotavirus and norovirus (NoV) infections among children amp;lt;5 years hospitalized (n=154) because of acute diarrhea in Ouagadougou, Burkina Faso, from December 2012 to November 2013, just before the start of vaccination. Overall, 44% and 23% of fecal samples were positive for rotavirus and NoV, respectively, most of them detected during the cold dry season (December-March). The predominant G/P combinations were G12P[8] (47%) and G6P[6] (30%). G2P[4] (n=3), G12P[6] (n=3), and G6P[8] (n=1) werealso detected. Nearly all (94%) successfully genotyped NoV strains belonged to genotype GII.4. The predominance of rotavirus and NoV was noteworthy in the age group 6 months, with 67% rotavirus and 22% NoV, respectively. Vomiting was significantly more common among rotavirus-infected children. To conclude, this study shows high detection rates of both rotavirus and NoV in children with severe diarrhea in Burkina Faso just before the introduction of rotavirus group A vaccination. The results can be used for estimating the impact of rotavirus group A vaccination, which started in the end of 2013. Furthermore, this study shows that the G6P[6] rotavirus strains emerging in Burkina Faso in 2010 is now established as a regionally important genotype.
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19.
  • Boström, Hans, et al. (författare)
  • U-2973, a novel B-cell line established from a patient with a mature B-cell leukemia displaying concurrent t(14;18) and MYC translocation to a non-IG gene partner
  • 2008
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 81:3, s. 218-225
  • Tidskriftsartikel (refereegranskat)abstract
    • B-cell lymphomas/leukemias with simultaneous t(14;18)(q32;q21) and MYC rearrangements have recently been shown to constitute a separate diagnostic entity, presenting with a rapid clinical course and a very poor prognosis. We describe the establishment of an Epstein-Barr virus negative cell line, designated U-2973, from a male patient with a de novo aggressive B-cell lymphoma/leukemia and very high peripheral blast cell count. Flow cytometry of bone marrow cells and U-2973 displayed a mature B-cell phenotype, and immunostaining showed expression of MYC and BCL2. IG gene rearrangement data were consistent with a lymphoid neoplasm of germinal centre derivation. Cytogenetic studies using conventional G-banding, fluorescent in situ hybridization, spectral karyotyping and single nucleotide polymorphism array demonstrated a complex karyotype with both a t(14;18) and double translocations between MYC and a non-IG gene partner located at chromosome 12p12.1.
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20.
  • Bucardo, Filemón, et al. (författare)
  • Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor a Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua
  • 2021
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 223:2, s. 278-286
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundChikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya.MethodsTo test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays.ResultsAfter adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively).ConclusionThis study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
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21.
  • Bucardo, Filemon, et al. (författare)
  • Asymptomatic Norovirus Infections in Nicaraguan Children and its Association With Viral Properties and Histo-blood Group Antigens
  • 2010
  • Ingår i: PEDIATRIC INFECTIOUS DISEASE JOURNAL. - : Williams and Wilkins. - 0891-3668 .- 1532-0987. ; 29:10, s. 934-939
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It has been previously reported that histo-blood group antigens (HBGAs) and particularly secretor status provides protection against symptomatic norovirus infection, but it remains unclear to what extent this includes asymptomatic infections in children. Methods: To explore whether HBGAs or certain viral genotypes are associated with asymptomatic norovirus infections in a pediatric population in Nicaragua, we investigated 163 children andlt;= 5 years of age, without a recent history of diarrhea (andlt;= 10 days). Results: Asymptomatic norovirus infections were observed in 11.7% (19/163), with children andlt;= 6 months of age being most frequently infected (16%). Of the 19 norovirus-positive children, 4 (21%) and 10 (53%) were infected with genogroups GI and GII, respectively, and 4 children (21%) were infected with viruses of both genogroups. Most children had andgt;= 10(6) viral genomes per gram of feces. Nucleotide sequence analysis (15/19) revealed uncommon genotypes, such as, GII. 7 (n = 5) and GII. 2 (n = 3). An interesting observation was the low frequency of norovirus GII. 4 strains among the asymptomatic children. AB blood type, Lewis a (Lea(a+b-)) phenotype and nonsecretor genotype (se(428)se(428)) were not found among the asymptomatic children, but they occurred in population controls. Conclusions: Frequency of asymptomatic norovirus infections was similar to that observed in symptomatic children from Nicaragua. Norovirus GII. 2 and GII. 7 were frequently detected but the globally dominating GII. 4 was infrequent. Host genetic factors previously observed to be associated with protection against symptomatic norovirus infection were not found in this study.
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22.
  • Bucardo, Filemon, et al. (författare)
  • Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (= 3, 4-7 and = 8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at = 4 days post vaccination (DPV). At = 4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (amp;gt;13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.
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23.
  • Bucardo, Filemon, et al. (författare)
  • Impact of vaccination on the molecular epidemiology and evolution of group A rotaviruses in Latin America and factors affecting vaccine efficacy
  • 2015
  • Ingår i: Infection, Genetics and Evolution. - : ELSEVIER SCIENCE BV. - 1567-1348 .- 1567-7257. ; 34, s. 106-113
  • Forskningsöversikt (refereegranskat)abstract
    • Despite high rotavirus (RV) vaccine coverage (similar to 83%) and good effectiveness (similar to 77%) against RV-diarrhea hospitalization, RV is still contributing to the burden of diarrhea that persists in hospital settings in several Latin American countries, where RV vaccination is being implemented. Due to the extensive genomic and antigenic diversity, among co-circulating human RV, a major concern has been that the introduction of RV vaccination could exert selection pressure leading to higher prevalence of strains not included in the vaccines and/or emergence of new strains, thus, reducing the efficacy of vaccination. Here we review the molecular epidemiology of RV in Latin America and explore issues of RV evolution and selection in light of vaccination. We further explore etiologies behind the large burden of diarrhea remaining after vaccination in some countries and discuss plausible reasons for vaccine failures. (C) 2015 Elsevier B.V. All rights reserved.
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24.
  • Bucardo, F., et al. (författare)
  • Large increase of rotavirus diarrhoea in the hospital setting associated with emergence of G12 genotype in a highly vaccinated population in Nicaragua.
  • 2015
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 21:6, s. 603.e1-603.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • Rotaviruses (RVs) are a major cause of severe diarrhoea in young children. Nicaragua introduced routine immunization with the pentavalent RV vaccine (RV5) in 2006, which greatly reduced the incidence of diarrhoea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhoea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titres for a subset of RV-infected (n = 137) and noninfected children (n = 52) were determined with an in-house enzyme-linked immunosorbent assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and noninfected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. A marked increase of RV was evident in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage.
  •  
25.
  • Bucardo, Filemon, et al. (författare)
  • Low Prevalence of Rotavirus and High Prevalence of Norovirus in Hospital and Community Wastewater after Introduction of Rotavirus Vaccine in Nicaragua
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city of Leon from July 2007 to July 2008 and compared these data with pre-vaccination data. The major finding was the low prevalence of RV compared to NoV in all sampling points (11% vs 44%, pandlt;0.05), and that RV concentration was lower as compared to NoV. RV was observed mainly during the rainy season (July-September), and the majority of all RV detected (6/9) belonged to subgroup (SG) I. The partial VP7-gene obtained from one RV positive sample was similar (99% nt identity) to a G6 VP7-gene of bovine origin and similar to the corresponding gene of the vaccine strain (98%). Furthermore RV G-types 2 and 4 were found in the incoming wastewater. NoV strains were detected throughout the year, of which a majority (20/21) were of genotype GII.4. We conclude that the introduction of RV vaccination reduced the transmission of RV in the community in Nicaragua. However, the burden of diarrhea in the country remains high, and the high prevalence of NoVs in hospital and municipal wastewater is noteworthy. This study highlights the need for further assessment of NoV following RV vaccine introduction.
  •  
26.
  • Bucardo, Filemon, et al. (författare)
  • Pediatric norovirus diarrhea in Nicaragua
  • 2008
  • Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 46:8, s. 2573-2580
  • Tidskriftsartikel (refereegranskat)abstract
    • Information about norovirus (NoV) infections in Central America is limited. Through a passive community and hospital pediatric diarrhea surveillance program, a total of 542 stool samples were collected between March 2005 and February 2006 in León, Nicaragua. NoV was detected in 12% (65/542) of the children; of these, 11% (45/409) were in the community and 15% (20/133) were in the hospital, with most strains (88%) belonging to genogroup II. NoV infections were age and gender associated, with children of <2 years of age (P < 0.05) and girls (P < 0.05) being most affected. Breast-feeding did not reduce the number of NoV infections. An important proportion (57%) of NoV-infected children were coinfected with diarrheagenic Escherichia coli. A significant proportion (18/31) of NoV-positive children with dehydration required intravenous rehydration. Nucleotide sequence analysis (38/65) of the N-terminal and shell region in the capsid gene revealed that at least six genotypes (GI.4, GII.2, GII.4, GII.7, GII.17, and a potentially novel cluster termed "GII.18-Nica") circulated during the study period, with GII.4 virus being predominant (26/38). The majority (20/26) of those GII.4 strains shared high nucleotide homology (99%) with the globally emerging Hunter strain. The mean viral load was approximately 15-fold higher in children infected with GII.4 virus than in those infected with other G.II viruses, with the highest viral load observed for the group of children infected with GII.4 and requiring intravenous rehydration. This study, the first of its type from a Central American country, suggests that NoV is an important etiological agent of acute diarrhea among children of <2 years of age in Nicaragua.
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27.
  • Bucardo, Filemon, et al. (författare)
  • Pediatric norovirus GII.4 infections in Nicaragua, 1999-2015
  • 2017
  • Ingår i: Infection, Genetics and Evolution. - : ELSEVIER SCIENCE BV. - 1567-1348 .- 1567-7257. ; 55, s. 305-312
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children amp;lt;= 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. Results: Norovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.
  •  
28.
  • Bucardo, Filemon, et al. (författare)
  • Predominance of Norovirus and Sapovirus in Nicaragua after Implementation of Universal Rotavirus Vaccination
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:5, s. e0098201-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite significant reduction of rotavirus (RV) infections following implementation of RotaTeq vaccination in Nicaragua, a large burden of patients with diarrhea persists. Methods: We conducted a community-and hospital-based study of the burden of RV, norovirus (NV) and sapovirus (SV) infections as cause of sporadic acute gastroenteritis (GE) among 330 children less than= 5 years of age between September 2009 and October 2010 in two major cities of Nicaragua with a RotaTeq coverage rate of 95%. Results: We found that NV, SV and RV infections altogether accounted for 45% of cases of GE. Notably, NV was found in 24% (79/330) of the children, followed by SV (17%, 57/330) and RV (8%, 25/330). The detection rate in the hospital setting was 27%, 15% and 14% for NV, SV and RV respectively, whereas in the community setting the detection rate of RV was less than 1%. Among each of the investigated viruses one particular genogroup or genotype was dominant; GII.4 (82%) for NV, GI (46%) for SV and G1P[8] (64%) in RV. These variants were also found in higher proportions in the hospital setting compared to the community setting. The GII.4.2006 Minerva strain circulating globally since 2006 was the most common among genotyped NV in this study, with the GII.4-2010 New Orleans emerging in 2010. Conclusions: This study shows that NV has become the leading viral cause of gastroenteritis at hospital and community settings in Nicaragua after implementation of RV vaccination.
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29.
  • Bucardo, F., et al. (författare)
  • Seroprevalence in Household Raised Pigs Indicate High Exposure to GII Noroviruses in Rural Nicaragua
  • 2016
  • Ingår i: Zoonoses and Public Health. - : WILEY-BLACKWELL. - 1863-1959 .- 1863-2378. ; 63:8, s. 600-607
  • Tidskriftsartikel (refereegranskat)abstract
    • Information about porcine norovirus (PoNoV), genetically similar to human NoV (HuNoV), is limited from rural areas where household-raised pigs are heavily exposed to faecal material which could facilitate transmission. Histoblood group antigens (HBGAs) are known susceptibility factors to NoV in humans and in a germfree piglet model but their role in susceptibility in the porcine population remains unknown. This study reports: (i) the seroprevalence and antibody titres to human norovirus (NoV) VLPs in household raised pigs; (ii) the distribution of HBGAs in relation to NoV IgG antibody titres and further characterization by blocking of GII. 4 VLP binding to pig gastric mucins (PGM). The majority of pigs were seropositive to all three VLPs tested (58-70%) with seropositivity and cross-reactivity increasing significantly with age. However, pig sera could not block the binding of NoV GII. 4 VLPs (Dijon) to PGM suggesting no previous infection with this genotype. The majority of the pigs were H-positive (84%), a susceptibility factor for human infections. IgG antibody titres were however higher in H-negative (GMT = 247) as compared with H-positive (GMT = 57) pigs, but after age stratification, this difference in antibody titres was only observed in pigs = 1 month of age. In conclusion, serological data show that the porcine population of Nicaragua is highly exposed to NoV infections, and the association to HBGAs warrants further investigation.
  •  
30.
  • Bucardo, Filemon, et al. (författare)
  • Susceptibility of Children to Sapovirus Infections, Nicaragua, 2005–2006
  • 2012
  • Ingår i: Emerging Infectious Diseases. - Atlanta, GA, USA : U.S. Department of Health and Human Services * Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:11, s. 1875-1878
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the genetic diversity of sapovirus (SaV) in children in Nicaragua and investigate the role of host genetic factors and susceptibility to SaV infections. Our results indicate that neither ABO blood group, Lewis phenotype, nor secretor status affects susceptibility to SaV infection in Nicaragua.
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31.
  • Bucardo, Filemon, et al. (författare)
  • The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine-take in Nicaraguan children
  • 2018
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are associated with susceptibility to rotavirus infection in a genotype-dependent manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor antigens were determined by saliva phenotyping and genotyping. Seroconversion was defined as a 4-fold increase in plasma IgA antibody titer 1 month after administration of the first dose of the vaccine. Regardless of the vaccine administered, significantly fewer of the children with Lewis A phenotype (0/14) seroconverted after receiving the first vaccine dose compared to 26% (45/175) of those with the Lewis B phenotype and 32% (15/47) of the Lewis negative individuals (P amp;lt; 0.01). Furthermore, following administration of the RV1 vaccine, secretor-positive ABO blood group B children seroconverted to a significantly lesser extent (5%) compared to secretor-positive children with ABO blood groups A (26%) and O (27%) (P amp;lt; 0.05). Other factors such as pre-vaccination titers, sex, breastfeeding, and calprotectin levels did not influence vaccine-take. Differences in HBGA expression appear to be a contributing factor in the discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic populations.
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32.
  • Bååth, Jonas, et al. (författare)
  • Trip Reports: Exploring the Experience of Psychedelic Intoxication
  • 2022
  • Ingår i: Handbook of Intoxicants and Intoxication. - London : Routledge. - 9780429058141 - 9780367178703 ; , s. 241-328
  • Bokkapitel (refereegranskat)abstract
    • Experiences of intoxication elude scientific research because of their immediate and ‘inner’ nature for the intoxicated individual. In this chapter, we show how ‘trip reports’ – reports of psychedelic intoxication – from online drug information forums and libraries allow for further understanding the experience of psychedelic intoxication from LSD, DMT and psilocybin by examining psychonauts’ (i.e., recreational psychedelic users) own understandings. Methods: The chapter draws on textual ethnography to analyze the trip rapports, approaching the reports as ‘native’ texts that allow for understanding constructions, conventions and practices of intoxication among participants in online psychonaut culture. We reviewed approximately 100 reports from three online drug information forums and libraries: Bluelight, Erowid and Shroomery. By focusing on nine of these reports, we demonstrate how they can be used to analyze psychedelic intoxication. Results: Our analysis shows how psychonauts construct their experiences by combining the context of psychedelic intoxication with inner aspects. The context refers to psychosocial factors of the psychonaut, such as expectations, and their material and social surroundings, such as interior design and other people present during intoxication. The inner experience refers to the arguably psychologically internal reactions and experiences of intoxicating effects, and how the psychonauts narrate them. Conclusions: Our findings show that intoxication follows observable patterns which may best be unraveled by approaching it as structured experience. Yet, the structure of these experiences is not necessarily framed in mystic or religious ways, suggesting that trip reports may complement current research on psychedelic intoxication that approaches it as religious or mystic experiences. Moreover, we suggest that further research should examine the systematics of context and inner experience of psychedelic intoxication which might aide the development of better methods for harm reduction and the study of the therapeutic potential of psychedelics.
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33.
  • Caliz, Joan, et al. (författare)
  • The microbiota of an unpolluted calcareous soil faces up chlorophenols: Evidences of resistant strains with potential for bioremediation
  • 2011
  • Ingår i: Chemosphere. - : Elsevier Science B.V., Amsterdam.. - 0045-6535 .- 1879-1298. ; 83:2, s. 104-116
  • Tidskriftsartikel (refereegranskat)abstract
    • To highlight the effects of a variety of chlorophenols (CP) in relation to the response of an indigenous bacterial community, an agricultural Mediterranean calcareous soil has been studied in microcosms incubated under controlled laboratory conditions. Soil samples were artificially polluted with 2-monochlorophenol (MCP), 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP), at concentrations ranging from 0.1 up to 5000 mg kg(-1). Both activity and composition of the microbial community were assessed during several weeks, respectively, by respirometric methods and PCR-DGGE analysis of extracted DNA and RNA. Significant decreases in soil respirometric values and changes in the bacterial community composition were observed at concentrations above 1000 mg kg(-1) MCP and TCP, and above 100 mg kg(-1) PCP. However, the persistence of several active bacterial populations in soil microcosms contaminated with high concentration of CP, as indicated by DGGE fingerprints, suggested the capacity of these native bacteria to survive in the presence of the pollutants, even without a previous adaptation or contact with them. The isolation of potential CP degraders was attempted by culture plating from microcosms incubated with high CP concentrations. Twenty-three different isolates were screened for their resistance to TCP and PCP. The most resistant isolates were identified as Kocuria palustris, Lysobacter gummosus, Bacillus sp. and Pseudomonas putida, according to 16S rRNA gene homology. In addition, these four isolates also showed the capacity to reduce the concentration of TCP and PCP from 15% to 30% after 5 d of incubation in laboratory assays (initial pollutant concentration of 50 mg L(-1)). Isolate ITP29, which could be a novel species of Bacillus, has been revealed as the first known member in this bacterial group with potential for CP bioremediation applications, usually wide-spread in the soil natural communities, which has not been reported to date as a CP degrader.
  •  
34.
  • Cantelli, Carina Pacheco, et al. (författare)
  • Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil
  • 2020
  • Ingår i: Infection, Genetics and Evolution. - : ELSEVIER. - 1567-1348 .- 1567-7257. ; 82
  • Tidskriftsartikel (refereegranskat)abstract
    • Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014-2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII.31, GII.P16 and GII.P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.
  •  
35.
  • Cantelli, Carina Pacheco, et al. (författare)
  • Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014-2018
  • 2020
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1(st)/2(nd) RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.
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36.
  • Dabrosin-Söderholm, Johan, 1958- (författare)
  • Epithelial barrier dysfunction in ileal Crohn's disease
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The study aimed at investigating the intestinal barrier in Crohn's disease, with special reference to epithelial responses to luminal stimuli, and to permeation of proteins.Ileal mucosa from patients undergoing intestinal resection was studied in vitro in Ussing chambers. Intestinal permeability was also studied in vivo, by oral load of lactulose and mannitol.The Ussing chamber was evaluated for intestinal barrier studies. Normal ileal mucosa from patients with colon cancer was subjected to long-term experiments, and investigated in regard to various viability parameters. Mucosal permeability, structural integrity and metabolism were maintained for 90 minutes, and specimens with poor viability were detected by a low transepithelial potential difference. In rat ileal mucosa, luminal sodium caprate, a constituent of milk fat, induced dilatation of the tight junctions as visualised by electron microscopy, and a reversible increase in tight junction permeability. The findings indicate that the Ussing chamber is suitable for studies of the intestinal barrier, including tight junction regulation, provided that experiments are monitored by measurements of transepithelial potential difference and are limited in time.In vitro studies of human ileal mucosa showed that luminal sodium caprate caused uncoupling of oxidative phosphorylation, as shown by a fall in epithelial ATP contents, and mitochondrial swelling seen by electron microscopy, paralleled by an increased permeability. Non-inflamed Crohn's disease specimens had an exaggerated permeability increase and an augmented fall in transepithelial electrical resistance. Confocal microscopy revealed rearrangements of perijunctional filamentous actin, causing dilatation of the tight junctions. In Crohn's disease, a more pronounced reorganisation of actin filaments was seen, suggesting the tight junctions to be hyperreactive to luminal stimuli due to a disturbed cytoskeletal regulation.In vivo, an increased intestinal permeability was induced by ingestion of acetylsalicylic acid. One third of both Crohn's disease patients and their first-degree relatives showed an augmented permeability increase, whereas spouses were equal to controls, suggesting a genetically determined vulnerability of the intestinal barrier.In vitro, non-inflamed ileum from Crohn's disease patients had an increased permeation of ovalbumin. Confocal microscopy suggested this to be caused by an augmented transcytosis, a previously unrecognised defect in the epithelial barrier in Crohn's disease, with a subsequent exposure of antigenic proteins to the subepithelial immunocytes.The Crohn's disease patients without residual inflammation after surgery were followed with endoscopy within twelve months, and all revealed recurrent ileal inflammation.The study indicates a perturbed intestinal barrier in Crohn's disease, possibly genetically determined. The impaired barrier function is demonstrated both by an augmented epithelial transcytosis and by hyperreactive tight junctions. The epithelial barrier dysfunction precedes the recurrent intestinal inflammation in ileal Crohn's disease. The findings suggest an interplay between an impaired epithelial barrier and luminal factors in the initiation of intestinal inflammation.
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37.
  • de Almeida, Nathalia Alves Araujo, et al. (författare)
  • Association between detection rate of norovirus GII and climatic factors in the Northwest Amazon region
  • 2024
  • Ingår i: Heliyon. - : CELL PRESS. - 2405-8440. ; 10:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Worldwide, approximately one fifth of all cases of diarrhea are associated with norovirus, mainly in children, with a defined seasonality in temperate climates, but seasonal dynamics are less known in tropical climates. The objective was to investigate the impact of external clinical, epidemiological, and climatic factors on norovirus detection rates in samples from children under 5 years of age from Roraima, the Amazon region of Brazil. A total of 941 samples were included. According to climatic factors, we observed correlations between external climatic factors and weekly positivity rates, where temperature (P = 0.002), relative humidity (P = 0.0005), absolute humidity (P < 0.0001) and wind speed had the strongest effect (P = 0.0006). The Brazilian Amazon region presents a typical and favorable scenario for the persistence, expansion, and distribution of viral gastroenteritis. Importance: This study is important as it will serve as a basis for studies carried out in Brazil and Latin American countries on the epidemiological importance, seasonality, climate change, antigenic diversity, among other factors in the circulation of gastroenteric virus.
  •  
38.
  • de Graaf, M., et al. (författare)
  • Emergence of a novel GII.17 norovirus - End of the GII.4 era?
  • 2015
  • Ingår i: Eurosurveillance. - : EUR CENTRE DIS PREVENTION and CONTROL. - 1025-496X .- 1560-7917. ; 20:26, s. 21178-
  • Tidskriftsartikel (refereegranskat)abstract
    • In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.
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39.
  • de Moraes, Marcia Terezinha Baroni, et al. (författare)
  • G6P[8] Rotavirus a Possessing a Wa-like VP3 Gene from a Child with Acute Gastroenteritis Living in the Northwest Amazon Region
  • 2023
  • Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 12:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of rotavirus A (RVA) vaccines has considerably reduced the RVA-associated mortality among children under 5 years of age worldwide. The ability of RVA to reassort gives rise to different combinations of surface proteins G (glycoprotein, VP7) and P (protease sensitive, VP4) RVA types infecting children. During the epidemiological surveillance of RVA in the Northwest Amazon region, an unusual rotavirus genotype G6P[8] was detected in feces of a 2-year-old child with acute gastroenteritis (AGE) that had been vaccinated with one dose of Rotarix(& REG;) (RV1). The G6P[8] sample had a DS-1-like constellation with a Wa-like VP3 gene mono-reassortment similar to equine-like G3P[8] that has been frequently detected in Brazil previously. The results presented here reinforce the evolutionary dynamics of RVA and the importance of constant molecular surveillance.
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40.
  • de Moraes, Marcia Terezinha Baroni, et al. (författare)
  • Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region
  • 2021
  • Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 10:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 (n = 3), GI.2 (n = 7), GII.1 (n = 1), GII.2 (n = 1), GII.3 (n = 5), GII.5 (n = 1), and GIV.1 (n = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.
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41.
  •  
42.
  • Duda, Laurent, et al. (författare)
  • Resonant Inelastic X-Ray Scattering at the Oxygen K Resonance of NiO: Nonlocal Charge Transfer and Double-Singlet Excitations
  • 2006
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 96:067402
  • Tidskriftsartikel (refereegranskat)abstract
    • We report high-resolution polarization-dependent resonant inelastic x-ray scattering (RIXS) at the O K resonance of NiO showing a rich excitation spectrum. We perform multisite Ni6O19 cluster model calculations, revealing that solid state effects are substantial. We identify a nonlocal charge transfer excitation at 4–5 eV and double-singlet creation at 1.75 eV, both exhibiting significant scattering geometry dependence. Apart from an intense band of local charge transfer excitations (above 5 eV) also dd excitations at 1 eV are observed. Finally, we point out that O K RIXS of correlated metal oxides allows a quantitative and consistent determination of the charge transfer energy and the Hund coupling energy JH.
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43.
  •  
44.
  • Esteves, A., et al. (författare)
  • Genetic diversity of norovirus in children under 5 years of age with acute gastroenteritis from Angola
  • 2018
  • Ingår i: Epidemiology and Infection. - : CAMBRIDGE UNIV PRESS. - 0950-2688 .- 1469-4409. ; 146:5, s. 551-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Norovirus (NoV) is a major cause of acute gastroenteritis (AGE). In this study, we investigated the genetic diversity of NoV strains identified in children under 5 years of age with AGE in four provinces of Angola. Faecal samples from 343 children were screened for NoV by an in house real-time PCR assay and genotyping was performed by partial capsid gene sequencing. NoV was detected in 17.4% (58/334) of the samples, with high detection rates in children amp;lt;6 months old (19%) and in children aged 12-24 months (23%). Genotype diversity was large, as demonstrated by the 11 identified genotypes. GII.4 was the predominant genotype (20% of all NoV-positive samples), followed by GII.6 (15%), GI.3 (12%), GII.7 (10%) and by other genotypes to a lesser extent. Two GII.4 variants, New Orleans 2009 and Sydney 2012, were detected and several genetic clusters were observed for genotypes GI.3, GII.6 and GII.7. The present study shows high detection rates and genetic diversity of circulating NoV genotypes in paediatric AGE samples from Angola. This information emphasises the importance of continuous assessment of NoV burden and evolution in the target population.
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45.
  • Esteves, Aida, et al. (författare)
  • Molecular Epidemiology of Rotavirus in Four Provinces of Angola Before Vaccine Introduction
  • 2016
  • Ingår i: Journal of Medical Virology. - : WILEY-BLACKWELL. - 0146-6615 .- 1096-9071. ; 88:9, s. 1511-1520
  • Tidskriftsartikel (refereegranskat)abstract
    • Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. (C) 2016 Wiley Periodicals, Inc.
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46.
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47.
  • Forsberg, Johan, 1974- (författare)
  • In Situ Soft X-ray Spectroscopies Applied to Atmospheric Corrosion And Related Systems
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis concerns the application of various soft x-ray spectroscopic methods (soft x-ray absorption, SXA, and emission, SXE) to complex, non-vacuum compatible systems, including liquids and multi-phase systems. The design, construction, and application of new instrumentation for in situ spectroscopy is described in detail. This includes sample holders using thin soft x-ray transparent membranes to enable measurements on systems completely isolated from vacuum, enabling flow of e.g. liquid or gas. In particular, a versatile setup for time resolved in situ chemical contrast x-ray transmission microscopy (CCXTM) was constructed and implemented. These instruments are expected to be applicable to a wide range of situations, for example in situ studies of chemical reactions, or biological specimen. The main project concerns atmospheric corrosion of iron in a saline environment, a process that requires the simultaneous presence of the solid (iron, NaCl), liquid (water) and gaseous (air) phases. It is also a highly inhomogeneous process, where lateral and time resolution is important. Using the CCXTM instrumentation, we were able to follow the distribution of all present elements over the sample with time resolution of a few minutes, and also to extract significant chemical information from the absorption edges. We observed e.g. the initial formation of corrosion products and transport of chlorine. Results from SXE measurements on water molecules in micelle structures are presented. A comparison with calculations reveal influence from the counter-ions, but also some spectral changes that may be attributed to water confinement. Also presented are angle dependent soft x-ray emission of liquid water, measuring scattered x-rays from different directions respect to the incident x-ray polarization. Existing preliminary theoretical expectations for the polarization dependence are contradictory. Our experiments show that a small angular anisotropy seems to be retained from the free molecule case.
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48.
  • Forsberg, Johan, et al. (författare)
  • System for in situ studies of atmospheric corrosion of metal films using soft x-ray spectroscopy and quartz crystal microbalance
  • 2007
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 78:8
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a versatile chamber (atmospheric corrosion cell) for soft x-ray absorption/emission spectroscopy of metal surfaces in a corrosive atmosphere allowing novel in situ electronic structure studies. Synchrotron x rays passing through a thin window separating the corrosion cell interior from a beamline vacuum chamber probe a metal film deposited on a quartz crystal microbalance (QCM) or on the inside of the window. We present some initial results on chloride induced corrosion of iron surfaces in humidified synthetic air. By simultaneous recording of QCM signal and soft x-ray emission from the corroding sample, correlation between mass changes and variations in spectral features is facilitated.
  •  
49.
  • Garcia, Marina, et al. (författare)
  • Innate lymphoid cells are activated in HFRS, and their function can be modulated by hantavirus-induced type I interferons
  • 2024
  • Ingår i: PLoS Pathogens. - : PUBLIC LIBRARY SCIENCE. - 1553-7366 .- 1553-7374. ; 20:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Hantaviruses cause the acute zoonotic diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Infected patients show strong systemic inflammation and immune cell activation. NK cells are highly activated in HFRS, suggesting that also other innate lymphoid cells (ILCs) might be responding to infection. Here, we characterized peripheral ILC responses, and measured plasma levels of soluble factors and plasma viral load, in 17 Puumala virus (PUUV)-infected HFRS patients. This revealed an increased frequency of ILC2 in patients, in particular the ILC2 lineage-committed c-Kitlo ILC2 subset. Patients' ILCs showed an activated profile with increased proliferation and displayed altered expression of several homing markers. How ILCs are activated during viral infection is largely unknown. When analyzing PUUV-mediated activation of ILCs in vitro we observed that this was dependent on type I interferons, suggesting a role for type I interferons-produced in response to virus infection-in the activation of ILCs. Further, stimulation of na & iuml;ve ILC2s with IFN-beta affected ILC2 cytokine responses in vitro, causing decreased IL-5 and IL-13, and increased IL-10, CXCL10, and GM-CSF secretion. These results show that ILCs are activated in HFRS patients and suggest that the classical antiviral type I IFNs are involved in shaping ILC functions. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are acute zoonotic diseases caused by orthohantaviruses. Hantavirus initially infect the lung and then spread systemically, primarily infecting endothelial cells. The innate lymphoid cell (ILC) family consists of ILC1, ILC2, ILC3, and natural killer (NK) cells. While NK cells are well studied in viral infections, less is known regarding the other ILCs. Hantavirus-infected patients show highly activated immune cells, including NK cells, indicating that also other innate lymphoid cells (ILCs) might be affected. We discovered that Puumala virus (PUUV)-infected HFRS patients show increased frequency of ILC2s in circulation, and that ILCs are activated with an altered homing receptor expression pattern. Little is known regarding how ILCs are activated during viral infection. When analyzing, in vitro, for mechanisms behind activation we observed a PUUV-induced type I IFN-dependent activation of ILCs and that IFN-beta affects ILC2 cytokine responses. These findings suggest that ILC functions are affected by classical antiviral type I IFNs.
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50.
  • Gia Phan, Tung, et al. (författare)
  • New astrovirus in human feces from Burkina Faso
  • 2014
  • Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 60:2, s. 161-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A significant fraction of cases of diarrhea, a leading cause of childhood mortality worldwide, remain unexplained. Objectives: To identify viruses in unexplained cases of diarrhea using an unbiased metagenomics approach. Study design: Viral nucleic acids were enriched from the feces from 48 cases of unexplained diarrhea from Burkina Faso, sequenced, and compared against all known viral genomes. Results: The full genome of a highly divergent astrovirus was sequenced in a sample co-infected with parechovirus 1. RT-PCR identified a single astrovirus infection in these 48 patients indicating a low prevalence. Human astrovirus-BF34 was most closely related to mamastrovirus species 8 and 9 also found in human with which it shared 62%, 74%, and 57% amino acid identities over its protease, RNA dependent RNA polymerase and capsid proteins, respectively. Conclusions: Burkina Faso astrovirus is proposed as prototype for a novel species in the genus Mamastrovirus, here tentatively called Mamastrovirus 20, representing the fifth human astrovirus species.
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