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| 2. |
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| 3. |
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| 4. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Eijsbouts, C., et al.
(författare)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 6. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 7. |
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| 8. |
- Wightman, D. P., et al.
(författare)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 9. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 10. |
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| 11. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 12. |
- Muthukkaruppan, V. R., et al.
(författare)
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Monoclonal antibodies against Salmonella porins : generation and characterization
- 1992
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Ingår i: Immunology Letters. - Amsterdam : Elsevier. - 0165-2478 .- 1879-0542. ; 33:2, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies (mAbs) were generated against porins, one of the major outer membrane proteins of Salmonella typhi. Six clones, designated MP1, MP2, MP3 (IgG2ak), MPN4, MPN6 (IgG1k) and MPN5 (IgG2bk) were characterized by enzyme immunoassay (ELISA) for their reactivity to porins from S. typhi, Salmonella paratyphi A, S. paratyphi B, S. paratyphi C, Salmonella choleraesuis, Salmonella enteritidis, Salmonella krefeld, Salmonella panama, Salmonella typhimurium, Escherichia coli B, Shigella flexneri 1b and Pseudomonas aeruginosa. All the clones positive for S. typhi porins showed varying reactivity towards several Salmonella species. However, none of them was positive for porins from other Gram-negative bacteria or for lipopolysaccharide (LPS). The affinity constant of these mAbs, except MPN4, was found to be in the higher range. Dot ELISA revealed that the mAbs recognized porins only in their native form. The results of inhibition ELISA using horseradish peroxidase (HRP)-conjugated MP1 suggest that the clones MP1, MP2, MP3, MPN5 and MPN6 secreted antibodies to identical epitope(s) of a 36-kDa peptide and MPN4 to a different epitope of a 35-kDa peptide. The possible applications of these mAbs were discussed.
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| 13. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
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Diagnosis of typhoid fever : detection of Salmonella typhi porins-specific antibodies by inhibition ELISA
- 1993
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Ingår i: Clinical and Experimental Immunology. - Chichester : Wiley-Blackwell Publishing Inc.. - 0009-9104 .- 1365-2249. ; 94:2, s. 317-321
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Tidskriftsartikel (refereegranskat)abstract
- Porins are highly immunogenic outer membrane proteins of Salmonella. Sera from typhoid patients contained a high level of IgG antibodies directed to porins of Salm. typhi. Since porins are highly conserved proteins, anti-porins antibodies both from typhoid patients and healthy normals reacted with porins from several Gram-negative bacteria. Therefore, in order to improve the specificity of detecting Salm. typhi porins-specific antibodies, an inhibition ELISA was developed using enzyme-conjugated MoAbs (MP1 and MPN4) specific to Salm. typhi porins. Sera from typhoid patients with positive haemoculture (16 out of 17) inhibited the binding of MP1 to porins, thus showing a positive test for typhoid, whereas sera from patients with other Gram-negative bacterial infections (n = 7) and from healthy volunteers (66 out of 67) were found to be negative. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of this assay were 94.1, 98.7, 97.8, 94.1 and 98.7% respectively. The validity of our inhibition ELISA for typhoid was higher than that of the Widal test. The diagnosis of typhoid fever as early as 3 days after the onset of fever, using a single specimen is possible.
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| 14. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 15. |
- Bijavara Seshashayana, Shilpa, et al.
(författare)
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Stellar Population Astrophysics (SPA) with TNG
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. The age, evolution, and chemical properties of the Galactic disk can be effectively ascertained using open clusters. Within the large program Stellar Populations Astrophysics at the Telescopio Nazionale Galileo, we specifically focused on stars in open clusters, to investigate various astrophysical topics, from the chemical content of very young systems to the abundance patterns of lesser studied intermediate-age and old open clusters.Aims. We investigate the astrophysically interesting element fluorine (F), which has an uncertain and intriguing cosmic origin. We also determine the abundance of cerium (Ce), as F abundance is expected to correlate with the s-process elements. We intend to determine the trend of F abundance across the Galactic disk as a function of metallicity and age. This will offer insights into Galactic chemical evolution models, potentially enhancing our comprehension of this element’s cosmic origin.Methods. High-resolution near-infrared spectra were obtained using the GIANO-B spectrograph. The Python version of Spectroscopy Made Easy (PySME), was used to derive atmospheric parameters and abundances. The stellar parameters were determined using OH, CN, and CO molecular lines along with Fe I lines. The F and Ce abundances were inferred using two K-band HF lines (λλ 2.28, 2.33 µm) and two atomic H-band lines (λλ 1.66, and 1.71 µm), respectively.Results. Of all the clusters in our sample, only King 11 had not been previously studied through medium- to high-resolution spectroscopy, and our stellar parameter and metallicity findings align well with those documented in the literature. We have successfully inferred F and Ce abundances in all seven open clusters and probed the radial and age distributions of abundance ratios. This paper presents the first F Galactic radial abundance gradient. Our results are also compared with literature estimates and with Galactic chemical evolution models that have been generated using different F production channels.Conclusions. Our results indicate a constant, solar pattern in the [F/Fe] ratios across clusters of different ages, supporting the latest findings that fluorine levels do not exhibit any secondary behavior for stars with solar or above-solar metallicity. However, an exception to this trend is seen in NGC 6791, a metal-rich, ancient cluster whose chemical composition is distinct due to its enhanced fluorine abundance. This anomaly strengthens the hypothesis that NGC 6791 originated in the inner regions of the Galaxy before migrating to its present position. By comparing our sample stars with the predictions of Galactic chemical evolution models, we came to the conclusion that both asymptotic giant branch stars and massive stars, including a fraction of fast rotators that increase with decreasing metallicity, are needed to explain the cosmic origin of F.
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| 16. |
- Fransen, M. F., et al.
(författare)
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A Restricted Role for FcgammaR in the Regulation of Adaptive Immunity
- 2018
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 200:8, s. 2615-2626
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Tidskriftsartikel (refereegranskat)abstract
- By their interaction with IgG immune complexes, FcgammaR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcgammaR-knockout mice, it has been concluded that FcgammaRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcgammaRs (FcgammaRI/II/III/IV(-/-) mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcgammaRIIb-deficient mice, FcgammaRI/II/III/IV(-/-) mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcgammaRs in the modulation of the adaptive immune response in vivo. We conclude that FcgammaRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity.
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| 17. |
- Iversen, M. B., et al.
(författare)
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An innate antiviral pathway acting before interferons at epithelial surfaces
- 2016
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:2, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.
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| 18. |
- Kessel, C., et al.
(författare)
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A single functional group substitution in c5a breaks B cell and T cell tolerance and protects against experimental arthritis
- 2014
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 66:3, s. 610-621
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A deficiency in C5 protects against arthritis development. However, there is currently no approach successfully translating these findings into arthritis therapy, as by targeting the key component, C5a. The aim of this study was to develop a vaccination strategy targeting C5a as therapy for patients with rheumatoid arthritis. METHODS: An anti-C5a vaccine was generated by incorporating the unnatural amino acid p-nitrophenylalanine (4NPA) into selected sites in the murine C5a molecule. C5a-4NPA variants were screened for their immunogenicity in mice on different arthritis-susceptible class II major histocompatibility complex (MHC) backgrounds. A candidate vaccine was tested for its impact on disease in a murine model of collagen-induced arthritis (CIA). Immunity toward endogenous C5a as well as type II collagen was monitored and characterized. RESULTS: Replacing a single tyrosine residue in position 35 (Y(35) ) with 4NPA allowed the generation of an anti-C5a vaccine, which partly protected mice against the development of CIA while strongly ameliorating the severity of clinical disease. Although differing in just 3 atoms from wild-type C5a (wtC5a), C5aY(35) 4NPA induced loss of T cell and B cell tolerance toward the endogenous protein in mice expressing class II MHC H-2(q) molecules. Despite differential B cell epitope recognition, antibodies induced by both wtC5a and C5aY(35) 4NPA neutralized C5a. Thus, anti-wtC5a IgG titers during arthritis priming were potentially of critical importance for disease protection, because high titers of C5a-neutralizing antibodies after disease onset were unable to reverse the course of arthritis. CONCLUSION: The results of this study suggest that the most effective anti-C5a treatment in arthritis can be accomplished using a preventive vaccination strategy, and that treatment using conventional biologic or small molecule strategies targeting the C5a/C5aR axis may miss the optimal window for therapeutic intervention during the subclinical priming phase of the disease.
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| 19. |
- Kumar, Ashok, et al.
(författare)
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Integrated bioprocess for the production and isolation of urokinase from animal cell culture using supermacroporous cryogel matrices
- 2006
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Ingår i: Biotechnology and Bioengineering. - Hoboken, NJ : Wiley. - 1097-0290 .- 0006-3592. ; 93:4, s. 636-646
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Tidskriftsartikel (refereegranskat)abstract
- An integrated cell cultivation and protein product separation process was developed using a new type of supermacroporous polyacrylamide gel, called cryogel (pAAm-cryogel) support matrix. Human fibrosarcoma HT1080 and human colon cancer HCT116 cell lines were used to secrete urokinase (an enzyme of immense therapeutic utility) into the culture medium. The secreted protein was isolated from the circulating medium using a chromatographic capture column. A pAAm cryogel support with covalently coupled gelatin (gelatin-pAAm cryogel) was used for the cultivation of anchorage dependent cells in the continuous cell culture mode in 5% carbon dioxide atmosphere. The cells were attached to the matrix within 4-6 h of inoculation and grew as a tissue sheet inside the cryogel matrix. Continuous urokinase secretion into the circulating medium was monitored as a parameter of growth and viability of cells inside the bioreactor. No morphological changes were observed in the cells eluted from the gelatin-cryogel support and re-cultured in T-flask. The gelatin-pAAm cryogel bioreactor was further connected to a pAAm cryogel column carrying Cu(II)-iminodiacetic acid (Cu(II)-IDA)-ligands (Cu(II)-IDA-pAAm cryogel), which had been optimized for the capture of urokinase from the conditioned medium of the cell lines. Thus an automated system was built, which integrated the features of a hollow fiber reactor with a chromatographic protein separation system. The urokinase was continuously captured by the Cu(II)-IDA-pAAm cryogel column and periodically recovered through elution cycles. The urokinase activity increased from 250 PU/mg in the culture fluid to 2,310 PU/mg after recovery from the capture column which gave about ninefold purification of the enzyme. Increased productivity was achieved by operating integrated bioreactor system continuously for 32 days under product inhibition free conditions during which no back-pressure or culture contamination was observed. A total 152,600 Plough units of urokinase activity was recovered from 500 mL culture medium using 38 capture columns over a period of 32 days. (c) 2006 Wiley Periodicals, Inc.
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| 20. |
- Kutty Selva, Nandakumar, et al.
(författare)
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Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis.
- 2007
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Ingår i: European Journal of Immunology. - Weinheim : Wiley. - 1521-4141 .- 0014-2980. ; 37:10, s. 2973-2982
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Tidskriftsartikel (refereegranskat)abstract
- The glycosylation status of IgG has been implicated in the pathology of rheumatoid arthritis. Earlier, we reported the identification of a novel secreted endo-beta-N-acetylglucosaminidase (EndoS), secreted by Streptococcus pyogenes that specifically hydrolyzes the beta-1,4-di-N-acetylchitobiose core of the asparagine-linked glycan of human IgG. Here, we analyzed the arthritogenicity of EndoS-treated collagen type II (CII) -specific mouse mAb in vivo. Endoglycosidase treatment of the antibodies inhibited the induction of arthritis in (BALB/c x B10.Q) F1 mice and induced a milder arthritis in B10.RIII mice as compared with the severe arthritis induced by non-treated antibodies. Furthermore, EndoS treatment did not affect the binding of IgG to CII and their ability to activate complement, but it resulted in reduced IgG binding to Fc gamma R and disturbed the formation of stable immune complexes. Hence, the asparagine-linked glycan on IgG plays a crucial role in the development of arthritis.
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| 21. |
- Li, Yanpeng, et al.
(författare)
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Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthritis
- 2020
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Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antibodies binding to cartilage proteins are present in the blood and synovial fluid of early rheumatoid arthritis patients. In order to develop animal models mimicking the human disease, we have characterized the arthritogenic capacity of monoclonal antibodies directed towards different joint proteins in the cartilage.Methods: Purified antibodies specific to unmodified or citrullinated collagen type II (CII), collagen type XI (CXI), and cartilage oligomeric matrix protein (COMP) were produced as culture supernatant, affinity purified, pooled as antibody cocktails (Cab3 and Cab4), and injected intravenously into mice to induce arthritis. An adjuvant (lipopolysaccharide or mannan) was subsequently injected intraperitoneally on either day 5 or day 60 to enhance arthritis. Antibody binding and complement activation on the cartilage surface were analyzed by immunohistochemical methods. Bone erosions and joint deformations were analyzed by histological assessments, enzyme-linked immunosorbent assays, and micro-CT. Luminex was used to detect CII-triple helical epitope-specific antibody responses.Results: The new cartilage antibody cocktails induced an earlier and more severe disease than anti-CII antibody cocktail. Many of the mouse strains used developed severe arthritis with 3 antibodies, binding to collagen II, collagen XI, and cartilage oligomeric matrix protein (the Cab3 cocktail). Two new models of arthritis including Cab3-induced LPS-enhanced arthritis (lpsCAIA) and Cab3-induced mannan-enhanced arthritis (mCAIA) were established, causing severe bone erosions and bone loss, as well as epitope spreading of the B cell response. Cab4, with addition of an antibody to citrullinated collagen II, induced arthritis more efficiently in moderately susceptible C57BL/6 J mice.Conclusions: The new mouse model for RA induced with cartilage antibodies allows studies of chronic development of arthritis and epitope spreading of the autoimmune response and bone erosion.
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| 22. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
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Influence of immunopotentiators on the antiporin immunoglobulin G subclass : distribution and protective immunity against murine salmonellosis
- 1999
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Ingår i: Scandinavian Journal of Immunology. - Chichester : Wiley-Blackwell Publishing Inc.. - 0300-9475 .- 1365-3083. ; 50:2, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- To improve the immune potential of porin (a pore-forming protein of Salmonella sp.), different immunopotentiators such as Freund's complete adjuvant (FCA), lipopolysaccharide (LPS) and polyoxydonium (PO) were evaluated by studying the nature of the protective immune response induced against murine Salmonellosis. The nontoxic, synthetic heteropolymer polyoxydonium was as good as LPS at inducing antiporin immunoglobulin G (IgG) antibodies and protective immunity. Analysis of the antiporin IgG subclass pattern revealed a preferential increase in a particular subclass based on the immunopotentiator used. Porin, alone or emulsified in FCA, elicited predominantly antiporin IgG1 antibodies, whereas LPS preferentially evoked antiporin IgG2a, IgG2b and IgG3 antibodies. Polyoxydonium induced a clear shift towards antiporin IgG2b antibodies. The significance of these antiporin IgG subclass antibodies in protection against murine Salmonellosis was studied by passive immunization and by analysing the infected mouse sera.
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| 23. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
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Upregulation of antitumor immunity by IL-12 gene-transfected AK-5 tumor cells in vivo
- 1999
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Ingår i: Cytokines, cellular & molecular therapy. - Abingdon : Taylor & Francis. - 1368-4736 .- 1471-177X. ; 5:1, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- We have earlier demonstrated a significant role for IL-12 in the regression of a rat histiocytic tumor, AK-5. In order to analyze further the antitumor immunity induced by interleukin (IL)-12, we have established IL-12-secreting tumor cell clones by gene transfection. Significant enhancement in the lytic potential of splenocytes by the culture supernatants containing IL-12 demonstrated retention of biological activity by the tumor-cell-derived cytokine. Athymic nude mice transplanted subcutaneously with tumor cells engineered to secret IL-12 showed a significant reduction in tumor size, with enhanced antibody-dependent cellular cytotoxicity. Analysis of the serum samples from animals injected with the IL-12 gene-transfected AK-5 cells on different days revealed a significant increase in circulatory IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and antitumor antibodies, all of which contributed to the reduction in tumor mass. The enhanced proliferative capacity of splenocytes from these animals indicated the presence of highly activated immune cells in vivo. Similarly, intraperitoneal transplantation of IL-12 gene-transfected tumor cells in syngeneic Wistar rats induced a significant increase in cellular cytotoxicity, with a concomitant reduction in circulatory IL-12 (p40) protein. Administration of antibodies to IL-12 and IFN-gamma reduced the expression of the costimulatory molecules B7.1 and B7.2 and the cytolytic effectors granzyme B and Fas-L, suggesting their involvement in IFN-gamma-dependent antitumor immune response induced by IL-12. The present study thus demonstrates that IL-12 gene therapy could be among the promising approaches for an effective cancer therapy.
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| 24. |
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| 25. |
- Seshashayana, S. Bijavara, et al.
(författare)
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Stellar Population Astrophysics (SPA) with TNG : Fluorine abundances in seven open clusters
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. The age, evolution, and chemical properties of the Galactic disk can be effectively ascertained using open clusters. Within the large program Stellar Populations Astrophysics at the Telescopio Nazionale Galileo, we specifically focused on stars in open clusters, to investigate various astrophysical topics, from the chemical content of very young systems to the abundance patterns of lesser studied intermediate-age and old open clusters. Aims. We investigate the astrophysically interesting element fluorine (F), which has an uncertain and intriguing cosmic origin. We also determine the abundance of cerium (Ce), as F abundance is expected to correlate with the s-process elements. We intend to determine the trend of F abundance across the Galactic disk as a function of metallicity and age. This will offer insights into Galactic chemical evolution models, potentially enhancing our comprehension of this element's cosmic origin. Methods. High-resolution near-infrared spectra were obtained using the GIANO-B spectrograph. The Python version of Spectroscopy Made Easy (PySME), was used to derive atmospheric parameters and abundances. The stellar parameters were determined using OH, CN, and CO molecular lines along with Fe I lines. The F and Ce abundances were inferred using two K-band HF lines (λλ 2.28, 2.33 μm) and two atomic H-band lines (λλ 1.66, and 1.71 μm), respectively. Results. Of all the clusters in our sample, only King 11 had not been previously studied through medium-to high-resolution spectroscopy, and our stellar parameter and metallicity findings align well with those documented in the literature. We have successfully inferred F and Ce abundances in all seven open clusters and probed the radial and age distributions of abundance ratios. This paper presents the first F Galactic radial abundance gradient. Our results are also compared with literature estimates and with Galactic chemical evolution models that have been generated using different F production channels. Conclusions. Our results indicate a constant, solar pattern in the [F/Fe] ratios across clusters of different ages, supporting the latest findings that fluorine levels do not exhibit any secondary behavior for stars with solar or above-solar metallicity. However, an exception to this trend is seen in NGC 6791, a metal-rich, ancient cluster whose chemical composition is distinct due to its enhanced fluorine abundance. This anomaly strengthens the hypothesis that NGC 6791 originated in the inner regions of the Galaxy before migrating to its present position. By comparing our sample stars with the predictions of Galactic chemical evolution models, we came to the conclusion that both asymptotic giant branch stars and massive stars, including a fraction of fast rotators that increase with decreasing metallicity, are needed to explain the cosmic origin of F.
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