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Plasmidless, photosynthetically incompetent mutants of Rhodospirillum rubrum 总被引:1,自引:0,他引:1
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Ethyl methanesulfonate rendered a high percentage of Rhodospirillum rubrum cells plasmidless and photosynthetically incompetent (Kuhl et al., J. Bacteriol. 156:737-742, 1983). By probing restriction endonuclease-digested chromosomal DNA from these plasmidless strains with 32P-labeled R. rubrum plasmid DNA, we showed that no homology exists between the plasmid and the chromosomal DNA of the mutant. Loss of the plasmid in all the nonphotosynthetic isolates was accompanied by the synthesis of spirilloxanthin under aerobic growth conditions, resistance to cycloserine and HgCl2, and loss of ability to grow fermentatively on fructose. Changes in both the protein and lipid composition of the membranes and the impaired uptake of 203HgCl2 in the plasmidless strains (compared with the wild type) suggest either that membrane modification occurs as a result of plasmid loss, accounting for several of the acquired phenotype characteristics of the cured strains, or that both membrane modification and plasmid loss are part of the same pleiotropic mutation. 相似文献
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Jing Zhou MD Pengfei Wu MM Hongyu Sun MM Hong Zhou BM Yaolei Zhang BM Zhenliang Xiao MD 《Journal of cellular physiology》2020,235(3):2377-2388
This study aimed to examine whether lung tissue extracellular matrix (ECM) hydrogels have protective effects on radiation-induced lung injury (RILI). The cytocompatibility and histocompatibility were tested for the obtained ECM-derived hydrogel. Sprague–Dawley rats were randomly divided into three groups (n = 18): control group (control); rats receiving irradiation and intratracheal injection of normal saline (IR + NS); and rats receiving irradiation and intratracheal injection of lung ECM-derived hydrogel (IR + ECM). The wet/dry weight ratio was used to evaluate the congestion and edema of the lungs. Histopathological analysis of lung tissues was performed using hemotoxylin and eosin staining and Masson's trichrome staining. Immunohistochemical staining and western blot analyses were carried out to determine the expression of epithelial–mesenchymal transition (EMT)-related proteins in lung tissues (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin). In addition, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6), hydroxyproline, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were also evaluated. The ECM-derived hydrogels had good cytocompatibility and histocompatibility. ECM-derived hydrogel treatment improved lung histopathology injury and pulmonary edema. Higher expression of E-cadherin and lower expression of vimentin and α-SMA were found in the IR + ECM group compared with those in the IR + NS group. Hydroxyproline levels were reduced by ECM-derived hydrogel treatment compared with those in the IR + NS group. Obvious increases of TNF-α, IL-6, and TGF-β1 were identified following irradiation. Marked reductions in MDA content and increases in SOD were induced by ECM-derived hydrogel treatment in rats after radiation. ECM-derived hydrogels were shown to protect against RILI, potentially by reducing EMT, inflammation, and oxidative damage. 相似文献
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van Beers JJ Raijmakers R Alexander LE Stammen-Vogelzangs J Lokate AM Heck AJ Schasfoort RB Pruijn GJ 《Arthritis research & therapy》2010,12(6):R219
Introduction
Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. 相似文献6.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献7.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88
Background
Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.Methods
We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.Results
Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.Conclusions
Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.8.
Buczek FL Sinsel EW Gloekler DS Wimer BM Warren CM Wu JZ 《Journal of biomechanics》2011,44(9):1805-1809
Upper extremity musculoskeletal disorders represent an important health issue across all industry sectors; as such, the need exists to develop models of the hand that provide comprehensive biomechanics during occupational tasks. Previous optical motion capture studies used a single marker on the dorsal aspect of finger joints, allowing calculation of one and two degree-of-freedom (DOF) joint angles; additional algorithms were needed to define joint centers and the palmar surface of fingers. We developed a 6DOF model (6DHand) to obtain unconstrained kinematics of finger segments, modeled as frusta of right circular cones that approximate the palmar surface. To evaluate kinematic performance, twenty subjects gripped a cylindrical handle as a surrogate for a powered hand tool. We hypothesized that accessory motions (metacarpophalangeal pronation/supination; proximal and distal interphalangeal radial/ulnar deviation and pronation/supination; all joint translations) would be small (less than 5° rotations, less than 2mm translations) if segment anatomical reference frames were aligned correctly, and skin movement artifacts were negligible. For the gripping task, 93 of 112 accessory motions were small by our definition, suggesting this 6DOF approach appropriately models joints of the fingers. Metacarpophalangeal supination was larger than expected (approximately 10°), and may be adjusted through local reference frame optimization procedures previously developed for knee kinematics in gait analysis. Proximal translations at the metacarpophalangeal joints (approximately 10mm) were explained by skin movement across the metacarpals, but would not corrupt inverse dynamics calculated for the phalanges. We assessed performance in this study; a more rigorous validation would likely require medical imaging. 相似文献
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B M Wimer 《Molecular biotherapy》1989,1(6):311-317
The current focus on interleukin-2 typifies the transition in cancer immunotherapy from nonspecific immunostimulants that are broadly supportive to highly defined cytokines with greater stress on treatment. With the introduction of lymphokine-activated killer cells, there was a parallel shift in emphasis from the use of allogeneic adoptive lymphocytes to in vitro expanded autologous cells. On the assumption that there should be a place for a more complete biological response modifier (BRM) applicable as a fundamental agent that would provide maximum support for all treatment modalities and that might facilitate the adoptive use of incompatible mononuclear cells when needed, an attempt was made to draw on the extensive experience with the large number of BRMs that have been studied to define the characteristics and therapeutic activities of an agent that would be ideally suited. It is ironic that the mitogenic lectins have tended to be overlooked in BRM classifications, but compelling evidence suggests that PHA-L4, the L4 isolectin of phytohemagglutinin, might at least partially fulfill all of the criteria of an ideal BRM. 相似文献
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Goedkoop AY Kraan MC Picavet DI de Rie MA Teunissen MB Bos JD Tak PP 《Arthritis research & therapy》2004,6(4):R326-R334
Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To
evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic
lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable
methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab
(3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable
methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity
Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies
from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4.
Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and
the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI
was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 (P ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady
decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction
in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of αvβ3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant
reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend
toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab
treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration
and clinical improvement in psoriasis and psoriatic arthritis. 相似文献