scholarly journals Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

2017 ◽  
Vol 114 (19) ◽  
pp. E3839-E3848 ◽  
Author(s):  
Jeffrey M. Harder ◽  
Catherine E. Braine ◽  
Pete A. Williams ◽  
Xianjun Zhu ◽  
Katharine H. MacNicoll ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Transcriptional Profiling ◽  
Early Time ◽  
Complement C3 ◽  
Egfr Signaling ◽  
Early Time Point ◽  
Complement Components ◽  
Iop Elevation ◽  
Time Point

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

scholarly journals Chronic mild and acute severe glaucomatous neurodegeneration derived from silicone oil-induced ocular hypertension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Fang ◽  
Jie Zhang ◽  
Pei Zhuang ◽  
Pingting Liu ◽  
Liang Li ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
High Frequency ◽  
Molecular Mechanisms ◽  
Silicone Oil ◽  
Early Time ◽  
Similar Degree ◽  
Pupillary Dilation ◽  
Early Time Point ◽  
Chronic Model ◽  
Iop Elevation

AbstractRecently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.

Transcriptional Profiling of Early and Late Phases of Bovine Tuberculosis.

2021 ◽  
Author(s):  
Hazem F. M. Abdelaal ◽  
Tyler C. Thacker ◽  
Bishoy Wadie ◽  
Mitchell V. Palmer ◽  
Adel M. Talaat
Keyword(s):  
Bovine Tuberculosis ◽  
Chemokine Receptors ◽  
Host Response ◽  
Control Strategies ◽  
Virulent Strain ◽  
Transcriptional Profiling ◽  
Early Time ◽  
Late Time ◽  
Potential Biomarker ◽  
Time Point

Bovine tuberculosis, caused by Mycobacterium tuberculosis var. bovis ( M. bovis ), is an important enzootic disease affecting mainly cattle, worldwide. Despite the implementation of national campaigns to eliminate the disease, bovine tuberculosis remains recalcitrant to eradication in several countries. Characterizing the host response to M. bovis infection is crucial for understanding the immunopathogenesis of the disease and for developing better control strategies. To profile the host responses to M. bovis infection, we analyzed the transcriptome of whole blood cells collected from experimentally infected calves with a virulent strain of M. bovis using RNA transcriptome sequencing (RNAseq). Comparative analysis of calf transcriptomes at early (8 weeks) vs. late (20 weeks) aerosol infection with M. bovis revealed divergent and unique profile for each stage of infection. Notably, at the early time point, transcriptional upregulation was observed among several of the top-ranking canonical pathways involved in T-cell chemotaxis. At the late time point, enrichment in the cell mediated cytotoxicity (e.g. Granzyme B) was the predominant host response. These results showed significant change in bovine transcriptional profiles and identified networks of chemokine receptors and monocyte chemoattractant protein (CCL) co-regulated genes that underline the host-mycobacterial interactions during progression of bovine tuberculosis in cattle. Further analysis of the transcriptomic profiles identified potential biomarker targets for early and late phases of tuberculosis in cattle. Overall, the identified profiles better characterized identified novel immunomodulatory mechanisms and provided a list of targets for further development of potential diagnostics for tuberculosis in cattle.

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

Salt induced programmed cell death in rice: evidence from chloroplast proteome signature

2021 ◽  
Vol 48 (1) ◽  
pp. 8
Author(s):  
Vivek Ambastha ◽  
Sudhir K. Sopory ◽  
Baishnab C. Tripathy ◽  
Budhi Sagar Tiwari
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Early Time ◽  
Biological Functions ◽  
Rice Seedlings ◽  
Early Time Point ◽  
Phosphorylation Pattern ◽  
Moderate Salinity ◽  
Chloroplast Proteome ◽  
Time Point

Soil salinity, depending on its intensity, drives a challenged plant either to death, or survival with compromised productivity. On exposure to moderate salinity, plants can often survive by sacrificing some of their cells ‘in target’ following a route called programmed cell death (PCD). In animals, PCD has been well characterised, and involvement of mitochondria in the execution of PCD events has been unequivocally proven. In plants, mechanistic details of the process are still in grey area. Previously, we have shown that in green tissues of rice, for salt induced PCD to occur, the presence of active chloroplasts and light are equally important. In the present work, we have characterised the chloroplast proteome in rice seedlings at 12 and 24 h after salt exposure and before the time point where the signature of PCD was observed. We identified almost 100 proteins from chloroplasts, which were divided in to 11 categories based on the biological functions in which they were involved. Our results concerning the differential expression of chloroplastic proteins revealed involvement of some novel candidates. Moreover, we observed maximum phosphorylation pattern of chloroplastic proteins at an early time point (12 h) of salt exposure.

scholarly journals Equivalent tumor detection for early and late FAPI-46 PET acquisition

2021 ◽  
Author(s):  
J. Ferdinandus ◽  
L. Kessler ◽  
N. Hirmas ◽  
M. Trajkovic-Arsic ◽  
R. Hamacher ◽  
...  
Keyword(s):  
Early Time ◽  
Tumor Detection ◽  
University Hospital ◽  
Late Time ◽  
Early Time Point ◽  
Positron Emission ◽  
Organ Uptake ◽  
Significant Difference ◽  
Late Time Point ◽  
Time Point

Abstract Introduction Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. Methods This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). Results In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: − 0.48, − 0.14, − 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03). Conclusion In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

C5a Depletion As a Novel Strategy to Inhibit T Regulatory Cells and Enhance Antigen-Specific Immune Responses

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3285-3285
Author(s):  
Suresh Veeramani ◽  
George J. Weiner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Regulatory Cells ◽  
Complement Components ◽  
Novel Strategy

Abstract Abstract 3285 Background: The complement system has complex activity that impacts on the immune response in a broad variety of ways. The current study was designed to assess the effect of complement components, specifically C5a, on the immune regulatory cells and on the development of an antigen-specific active immune response. Methods: Myeloid dendritic cells (mDCs), enriched from healthy human peripheral blood mononuclear cells, were pulsed with antigen (tetanus toxoid) and co-cultured with autologous, enriched human CD4+ T cells in the presence of various purified complement components. The percent of CD4+ T-cells that were CD25highFoxp3+ (henceforth referred to as Tregs) was determined. The presence of cytokines in supernatant of mDCs cultured with purified complement proteins was also evaluated. In murine models, the effect of C5a on in vivo induction of Tregs and on the development of immune response to ovalbumin was determined by analyzing anti-ovalbumin antibody. This was done in C5-sufficient (B10-D2-HC1) and C5-deficient (B10-D2-HC0) mice immunized with 100 μg of ovalbumin, and in wild type C57Bl/6 mice immunized with 100 μg of ovalbumin along with either irrelevant rat IgG2a (Ova+Isotype control) or rat anti-mouse C5a antibody (Ova+anti-C5a Ab). Results: In Vitro: In Vivo: Conclusions: Presence of C5a in the immune microenvironment results in increased generation of Treg cells and leads to dampening of antigen-specific immune responses. Absence or depletion of C5a results in a drop in the Tregs and a higher antigen-specific immune response. Ongoing studies are exploring the use of C5a depletion as a novel strategy to overcome the low immunogenicity of vaccines, such as cancer vaccines. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Targeted Nanoprobes Reveal Early Time Point Kinetics In Vivo by Time-Resolved MRI

Theranostics ◽  
2011 ◽  
Vol 1 ◽  
pp. 274-276 ◽  
Author(s):  
Ashwinkumar Bhirde ◽  
Ning Guo ◽  
Xiaoyuan Chen
Keyword(s):  
Early Time ◽  
Early Time Point ◽  
Time Resolved ◽  
Point Kinetics ◽  
Kinetics In Vivo ◽  
Time Point

scholarly journals Oral bacteriophages are maintained at high levels for months in individuals but infrequently transmitted between mothers and infants

2019 ◽  
Author(s):  
Clifford J. Beall ◽  
Rosalyn M. Sulyanto ◽  
Ann L. Griffen ◽  
Eugene J. Leys
Keyword(s):  
Oral Cavity ◽  
Nucleotide Diversity ◽  
Early Time ◽  
Detectable Level ◽  
First Year ◽  
Bacterial Genomes ◽  
Early Time Point ◽  
Multiple Strains ◽  
Metagenomic Assembly ◽  
Time Point

ABSTRACTIn this work, we exploit recent advances in metagenomic assembly and bacteriophage identification to describe the phage content of saliva from 5 mother-baby pairs sampled twice 7 - 11 months apart during the first year of the babies’ lives. We identify 25 phage genomes that are comprised of one to 71 contigs, with 16 having a single contig. At the detectable level, phage were sparsely distributed with the most common one being present in 4 of the 20 samples, derived from two mothers and one baby. However, if they were present in the early time point sample from an individual, they were also present in the later sample from the same person more frequently than expected by chance. The nucleotide diversity (π) in phage from the same sample or the same person was much lower than between different individuals, indicating dominance of one strain in each person. This was different from bacterial genomes, which had higher diversity indicating the presence of multiple strains within an individual. We identify likely bacterial hosts for 16 of the 25 phage, including an apparent inovirus that is capable of integrating in the dif site ofHaemophilusspecies. It appears that phage in the oral cavity are sparsely distributed, but can be maintained for months once acquired.

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