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Mita Das Marjan Boerma Jessica R. Goree Elise G. Lavoie Michel Fausther Igor B. Gubrij Amanda K. Pangle Larry G. Johnson Jonathan A. Dranoff 《PloS one》2014,9(4)
Rationale
Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease.Objective
We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH.Methods And Results
Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery.Conclusion
Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions. 相似文献74.
Kenneth H. Ely Mitsuo Matsuoka Matthew P. DeBerge Jessica A. Ruby Jun Liu Mark J. Schneider Yan Wang Young S. Hahn Richard I. Enelow 《PloS one》2014,9(9)
Virus infection triggers a CD8+ T cell response that aids in virus clearance, but also expresses effector functions that may result in tissue injury. CD8+ T cells express a variety of activating and inhibiting ligands, though regulation of the expression of inhibitory receptors is not well understood. The ligand for the inhibitory receptor, NKG2A, is the non-classical MHC-I molecule Qa1b, which may also serve as a putative restricting element for the T cell receptors of purported regulatory CD8+ T cells. We have previously shown that Qa1b-null mice suffer considerably enhanced immunopathologic lung injury in the context of CD8+ T cell-mediated clearance of influenza infection, as well as evidence in a non-viral system that failure to ligate NKG2A on CD8+ effector T cells may represent an important component of this process. In this report, we examine the requirements for induction of NKG2A expression, and show that NKG2A expression by CD8+ T cells occurs as a result of migration from the MLN to the inflammatory lung environment, irrespective of peripheral antigen recognition. Further, we confirmed that NKG2A is a mediator in limiting immunopathology in virus infection using mice with a targeted deletion of NKG2A, and infecting the mutants with two different viruses, influenza and adenovirus. In neither infection is virus clearance altered. In influenza infection, the enhanced lung injury was associated with increased chemoattractant production, increased infiltration of inflammatory cells, and significantly enhanced alveolar hemorrhage. The primary mechanism of enhanced injury was the loss of negative regulation of CD8+ T cell effector function. A similar effect was observed in the livers of mutant mice infected intravenously with adenovirus. These results demonstrate the immunoregulatory role of CD8+ NKG2A expression in virus infection, which negatively regulates T cell effector functions and contributes to protection of tissue integrity during virus clearance. 相似文献
75.
One of the biggest challenges facing evolutionary biologists is to identify and understand loci that explain fitness variation
in natural populations. This review describes how genetic (linkage) mapping with single nucleotide polymorphism (SNP) markers
can lead to great progress in this area. Strategies for SNP discovery and SNP genotyping are described and an overview of
how to model SNP genotype information in mapping studies is presented. Finally, the opportunity afforded by new generation
sequencing and typing technologies to map fitness genes by genome-wide association studies is discussed. 相似文献
76.
Fledgling Bachman’s Sparrows in a longleaf pine ecosystem: survival,movements, and habitat selection
Alexander C. Fish Christopher S. DePerno Jessica M. Schillaci Christopher E. Moorman 《Journal of Field Ornithology》2020,91(4):354-366
Fledgling ecology remains understudied for many passerine species, yet information about the fledgling life stage is critical for understanding full-annual life cycles and population recruitment. We examined the survival, habitat selection, and movements of fledgling Bachman’s Sparrows (Peucaea aestivalis) in a longleaf pine-wiregrass (Pinus palustris-Aristida stricta) community managed with frequent prescribed fire. We captured and marked 36 fledglings on the day of fledging and used radio-telemetry to relocate them daily until independence during three breeding seasons (2014–2016). We visually confirmed the status of fledglings as live or dead during daily relocations and determined causes of mortality. We measured vegetation characteristics at fledgling locations and compared them to the characteristics of vegetation at the locations of adult males. We used a Known Fates analysis in Program MARK to estimate fledgling survival, and generalized linear mixed effect models to determine habitat selection. Estimated fledgling survival until independence was 0.31 (SE = 0.08), with most mortality during the first 4 d post-fledging. Fledglings with longer wing chords had higher rates of survival than those with shorter wing chords, possibly due to an increased ability to evade predators. Fledgling movements were restricted primarily to natal territories. Fledgling Bachman’s Sparrows were located in areas with greater woody plant, forb, and grass cover and less bare ground than available in natal territories. Similar to fledglings of other songbirds, understory woody and herbaceous plants appear to provide critical cover for fledgling Bachman’s Sparrows, and maintenance of such cover should receive consideration in management plans for longleaf pine communities. 相似文献
77.
Amol A. Verma Tejasvi Hora Hae Young Jung Michael Fralick Sarah L. Malecki Lauren Lapointe-Shaw Adina Weinerman Terence Tang Janice L. Kwan Jessica J. Liu Shail Rawal Timothy C.Y. Chan Angela M. Cheung Laura C. Rosella Marzyeh Ghassemi Margaret Herridge Muhammad Mamdani Fahad Razak 《CMAJ》2021,193(23):E859
78.
Shingo Ishihara Jessica J. Bitner Greg H. Farley Eric T. Gillock 《Current microbiology》2013,66(4):337-343
We analyzed highly vancomycin-resistant Gram-positive bacteria isolated from the saliva of migratory songbirds captured, sampled, and released from a bird-banding station in western Kansas. Individual bacterial isolates were identified by partial 16S rRNA sequencing. Most of the bacteria in this study were shown to be Staphylococcus succinus with the majority being isolated from the American Robin. Some of these bacteria were shown to carry vanA, vanB, and vanC vancomycin-resistance genes and have the ability to form biofilms. One of the van gene-carrying isolates is also coagulase positive, which is normally considered a virulence factor. Other organisms isolated included Staphylococcus saprophyticus as well as Enterococcus gallinarum. Given the wide range of the American Robin and ease of horizontal gene transfer between Gram-positive cocci, we postulate that these organisms could serve as a reservoir of vancomycin-resistance genes capable of transferring to human pathogens. 相似文献
79.
Francesca Vittoria Sbrana Benedetta Fiordi Jessica Bordini Daniela Belloni Federica Barbaglio Luca Russo Lydia Scarfò Paolo Ghia Cristina Scielzo 《Journal of cellular and molecular medicine》2023,27(4):576-586
Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy. 相似文献
80.
Marika A. Schulhof Andrew E. Allen Eric E. Allen Natalie Mladenov John P. McCrow Natalie T. Jones Jessica Blanton Hamanda B. Cavalheri Drishti Kaul Celia C. Symons Jonathan B. Shurin 《Molecular ecology》2020,29(11):2080-2093
Warming, eutrophication (nutrient fertilization) and brownification (increased loading of allochthonous organic matter) are three global trends impacting lake ecosystems. However, the independent and synergistic effects of resource addition and warming on autotrophic and heterotrophic microorganisms are largely unknown. In this study, we investigate the independent and interactive effects of temperature, dissolved organic carbon (DOC, both allochthonous and autochthonous) and nitrogen (N) supply, in addition to the effect of spatial variables, on the composition, richness, and evenness of prokaryotic and eukaryotic microbial communities in lakes across elevation and N deposition gradients in the Sierra Nevada mountains of California, USA. We found that both prokaryotic and eukaryotic communities are structured by temperature, terrestrial (allochthonous) DOC and latitude. Prokaryotic communities are also influenced by total and aquatic (autochthonous) DOC, while eukaryotic communities are also structured by nitrate. Additionally, increasing N availability was associated with reduced richness of prokaryotic communities, and both lower richness and evenness of eukaryotes. We did not detect any synergistic or antagonistic effects as there were no interactions among temperature and resource variables. Together, our results suggest that (a) organic and inorganic resources, temperature, and geographic location (based on latitude and longitude) independently influence lake microbial communities; and (b) increasing N supply due to atmospheric N deposition may reduce richness of both prokaryotic and eukaryotic microbes, probably by reducing niche dimensionality. Our study provides insight into abiotic processes structuring microbial communities across environmental gradients and their potential roles in material and energy fluxes within and between ecosystems. 相似文献