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41.
Isabella Russo Monica Traversa Katia Bonomo Alessandro De Salve Luigi Mattiello Paola Del Mese Gabriella Doronzo Franco Cavalot Mariella Trovati Giovanni Anfossi 《Obesity (Silver Spring, Md.)》2010,18(4):788-797
Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors—guanosine 3′,5′‐cyclic monophosphate (cGMP) and adenosine 3′,5′‐cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet‐induced body‐weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6‐month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMAIR)); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD‐40 ligand (sCD‐40L) and soluble P‐selectin (sP‐selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8‐bromoguanosine 3′,5′‐cyclic monophosphate (8‐Br‐cGMP) and 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP) to reduce platelet aggregation in response to adenosine‐5‐diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body‐weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8‐Br‐cGMP, and 8‐Br‐cAMP to reduce ADP‐induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body‐weight target. Changes of platelet function correlated with changes of HOMAIR. Thus, in central obesity, diet‐induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity. 相似文献
42.
Valentina Ferrari Alison Tarke Hannah Fields Luca Ferrari Trevor Conley Franco Ferrari Zeynep Koşaloğlu-Yalçın Alessandro Sette Bjoern Peters Colin L. McCarthy Asad Bashey Dimitrios Tzachanis Edward D. Ball Tiffany N. Tanaka Rafael Bejar Thomas A. Lane Antonella Vitiello 《Cytotherapy》2021,23(4):320-328
Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34+) and normal (CD3+) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4+ response and 11 (34%) induced a CD8+ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients. 相似文献
43.
Bošnjak Z Džijan S Pavlinić D Perić M Ružman N Križan IR Lauc G Antolović-Požgain A Burazin J Vuković D 《Current microbiology》2012,64(6):552-560
The purpose of this study was to determine prevalence of Chlamydia trachomatis (Ct) urogenital infection and its serotype distribution from clinical samples in north-eastern Croatia. During a 3-year period,
2,379 urogenital samples were analyzed by real-time polymerase chain reaction (A group), while 4,846 genital swabs were analyzed
by direct fluorescent antibody test (B group). 132 Ct positive specimens were genotyped by omp1 gene sequencing. The prevalence rate of Ct was 3.2 % in A and 1 % in B group. The most prevalent chlamydial genotype was
E (44 %), followed by F (33 %), K (11.5 %), G (8 %), J/UW (5.3 %), D-IC (4.4 %), D-B120 (1.8 %), and B/IU, J/IU, Ia/IU (0.9
% each) serotypes. Single-nucleotide polymorphisms (SNPs) of omp1 gene were detected in E, K, and G serotypes. Some of these SNPs (C/T at position 272 and G/A at position 813 in E strain;
C/T at position 884 in D strain) might represent novel omp1 variants. 相似文献
44.
45.
Mate limitation in populations of the endangered Convolvulus lineatus L.: A case for genetic rescue?
Regina Berjano Perrine Gauthier Alessandro Fisogni David Doblas Virginie Pons John D. Thompson 《Journal for Nature Conservation》2013,21(5):334-341
In self-incompatible clonal plants, the spread of individual plants can exacerbate mate limitation to the point that it becomes a serious constraint on long-term population persistence, especially in small, isolated populations. In such species, it may be necessary to introduce new genetic material from other populations to restore seed production, a strategy termed “genetic rescue”. In this study we assess the potential pertinence of such genetic rescue in the clonal perennial plant Convolvulus lineatus L., whose populations are often highly reduced in spatial extent and are currently being fragmented by land development projects in Mediterranean France. To do so, we quantify fruit production in a range of populations of different size over four years and perform a series of hand-pollination experiments in natural populations to assess whether fruit set is limited by mate availability. We found that C. lineatus is a self-incompatible species that shows extremely low values of fruit set in natural populations and that a principal cause of this low fruit set is a lack of compatible pollen. This may be primarily due to clonal spread that causes individual populations to be comprised of patches containing one or very few incompatibility types. In small populations fragmented by human activities and which show an absence of fruit production, we thus argue that genetic rescue represents a promising conservation management strategy to avoid inevitable long-term future population decline. We discuss how best to introduce new genetic material into the study populations. 相似文献
46.
The ε-subunit of ATP-synthase is an endogenous inhibitor of the hydrolysis activity of the complex and its α-helical C-terminal domain (εCTD) undergoes drastic changes among at least two different conformations. Even though this domain is not essential for ATP synthesis activity, there is evidence for its involvement in the coupling mechanism of the pump. Recently, it was proposed that coupling of the ATP synthase can vary as a function of ADP and Pi concentration. In the present work, we have explored the possible role of the εCTD in this ADP- and Pi-dependent coupling, by examining an εCTD-lacking mutant of Escherichia coli. We show that the loss of Pi-dependent coupling can be observed also in the εCTD-less mutant, but the effects of Pi on both proton pumping and ATP hydrolysis were much weaker in the mutant than in the wild-type. We also show that the εCTD strongly influences the binding of ADP to a very tight binding site (half-maximal effect ≈ 1 nM); binding at this site induces higher coupling in EFOF1 and increases responses to Pi. It is proposed that one physiological role of the εCTD is to regulate the kinetics and affinity of ADP/Pi binding, promoting ADP/Pi-dependent coupling. 相似文献
47.
Paolo d’Errico Marina Boido Antonio Piras Valeria Valsecchi Elena De Amicis Denise Locatelli Silvia Capra Francesco Vagni Alessandro Vercelli Giorgio Battaglia 《PloS one》2013,8(12)
Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients. 相似文献
48.
Martina Grdiša Sandra Babić Martina Periša Klaudija Carović‐Stanko Ivan Kolak Zlatko Liber Marija Jug‐Dujaković Zlatko Satovic 《化学与生物多样性》2013,10(3):460-472
Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir. ) Sch.Bip. ) is a plant species endemic to the east Adriatic coast. The bioactive substance of Dalmatian pyrethrum is a natural insecticide, pyrethrin, a mixture of six active components (pyrethrins I and II, cinerins I and II, and jasmolins I and II). The insecticidal potential of pyrethrin was recognized decades ago, and dried and ground flowers have traditionally been used in Croatian agriculture and households. A total of 25 Dalmatian pyrethrum populations from Croatia were studied to determine the pyrethrin content and composition, and to identify distinct chemotypes. The total pyrethrin content ranged from 0.36 to 1.30% (dry flower weight; DW) and the pyrethrin I/pyrethrin II ratio ranged from 0.64 to 3.33%. The statistical analyses revealed that the correlations between the percentage of pyrethrin I and of all the other components were significant and negative. The total pyrethrin content was positively correlated with the percentage of pyrethrin I and negatively correlated with cinerin II. The multivariate analysis of the chemical variability enabled the identification of five chemotypes among 25 Dalmatian pyrethrum populations. The chemical characterization of indigenous Dalmatian pyrethrum populations may serve as a good background for future breeding and agricultural exploitation. 相似文献
49.
The niche is a necessary consideration when estimating habitable area and geographic range of a species. Modellers often examine the fundamental niche and the environmental requirements for plant species, ignoring interactions among species. In deserts, positive plant interactions are important drivers of biodiversity and structure communities through many mechanistic pathways including modifying environmental conditions. Thus, we tested the hypothesis that desert shrubs increase the geographical extent of some annual species because, through modifying the microclimate, they match the niche requirements of beneficiary species. We used the database of the Global Biodiversity Information Facility to construct MaxEnt species distribution models (SDM) with and without reported benefactor species within the Mojave Desert in California. We chose 20 annual species to be modeled including 10 species that had been previously reported in the literature as being facilitated (beneficiary) and 10 that had no record of being facilitated (unreported). Beneficiary annuals co‐occurred significantly more with benefactor shrubs than the unreported annual species. The inclusion of shrubs into SDMs significantly improved model predictability and geographic range for all the beneficiary annual species, but not for the unreported annual species. Thus, positive interactions are species specific and it is possible to determine annual species dependency on benefactor shrubs at the regional scale. The co‐occurrence of benefactor shrubs and annual species can be used as a proxy for facilitation and recent developments in SDM techniques encourage the inclusion of biotic interactions. Species distribution models should include estimates of facilitation because biotic interactions determine the niche of species and can have implications with a changing climate. 相似文献
50.
Vita Peri Boris Ajdukovic Paul Holland Balwant S. Tuana 《Molecular and cellular biochemistry》1994,130(1):57-65
Dystrophin is a high molecular weight protein present at low abundance in skeletal, cardiac and smooth muscle and in trace amounts in brain. In skeletal muscle, dystrophin is uniformly distributed along the inner surface of the plasma membrane. Biochemical fractionation studies have shown that all detectable skeletal muscle dystrophin is tightly associated with a complex of wheat germ agglutinin (WGA)-binding and concanavalin A (Con A) binding sarcolemmal glycoproteins. Absence of dystrophin is the primary biochemical defect in patients with Duchenne muscular dystrophy and leads to segmental necrosis of their skeletal myofibers. Although present in similar amounts in normal cardiac and skeletal muscle, the absence of dystrophin from cardiac muscle has less severe effects on the survival of cardiac cells. We have therefore examined whether there are differences in the properties of cardiac and skeletal dystrophin. We report that in contrast to skeletal muscle, cardiac dystrophin is distributed between distinct pools: a soluble cytoplasmic pool, a membrane-bound pool not associated with WGA-binding glycoproteins and a membrane-bound pool associated with WGA-binding glycoproteins. Cardiac dystrophin was not associated with any Con A binding glycoproteins. Immunohistochemical localization studies in isolated ventricular myocytes reveal a distinct punctate staining pattern for dystrophin, approximating to the level of the transverse tubule/Z-line and contrasting with the uniform sarcolemmal staining reported for skeletal muscle fibers. The distinct properties of cardiac dystrophin suggest unique roles for this protein in cardiac versus skeletal muscle function.Abbreviations Dys
Dystrophin
- T-tubule
Transverse tubule
- SDS-PAGE
Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis
- WGA
Wheat Germ Agglutinin
- Con A
Concanavalin A
- DHP
Dihydropyridine receptor
- FITC
Fluorescein Isothiocyanate Conjugate
- NAG
N-Acetyl-D-Glucosamine
- NP-40
NONIDET P-40
- PBS
Phosphate-Buffered Saline
- TBST
Tris Buffered Saline-Tween 相似文献