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

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.

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  

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.


Author(s):  
J. Ferdinandus ◽  
L. Kessler ◽  
N. Hirmas ◽  
M. Trajkovic-Arsic ◽  
R. Hamacher ◽  
...  

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.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
O. N. Shevtsova ◽  
V. K. Shevtsova

The proposed model describes in a quality way the process of tumor-imaging radiopharmaceuticalTc99m-MIBI distribution with taking into account radiopharmaceutical accumulation, elimination, and radioactive decay. The dependencies of concentration versus the time are analyzed. The model can be easily tested by the concentration data of the radioactive pharmaceuticals in the blood measured at early time point and late time point of the scanning, and the obtained data can be used for determination of the washout rate coefficient which is one of the existing oncology diagnostics methods.


2017 ◽  
Vol 114 (19) ◽  
pp. E3839-E3848 ◽  
Author(s):  
Jeffrey M. Harder ◽  
Catherine E. Braine ◽  
Pete A. Williams ◽  
Xianjun Zhu ◽  
Katharine H. MacNicoll ◽  
...  

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.


Author(s):  
Yuxiang Ge ◽  
Yixuan Li ◽  
Zixu Wang ◽  
Lan Li ◽  
Huajian Teng ◽  
...  

Mechanical compression is a double-edged sword for cartilage remodeling, and the effect of mechanical compression on chondrogenic differentiation still remains elusive to date. Herein, we investigate the effect of mechanical dynamic compression on the chondrogenic differentiation of human synovium-derived mesenchymal stem cells (SMSCs). To this aim, SMSCs encapsulated in agarose hydrogels were cultured in chondrogenic-induced medium with or without dynamic compression. Dynamic compression was applied at either early time-point (day 1) or late time-point (day 21) during chondrogenic induction period. We found that dynamic compression initiated at early time-point downregulated the expression level of chondrocyte-specific markers as well as hypertrophy-specific markers compared with unloaded control. On the contrary, dynamic compression applied at late time-point not only enhanced the levels of cartilage matrix gene expression, but also suppressed the hypertrophic development of SMSCs compared with unloaded controls. Taken together, our findings suggest that dynamic mechanical compression loading not only promotes chondrogenic differentiation of SMSCs, but also plays a vital role in the maintenance of cartilage phenotype, and our findings also provide an experimental guide for stem cell-based cartilage repair and regeneration.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Tsung-I Peng ◽  
Muh-Shi Lin ◽  
Mei-Jie Jou

Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ0) lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa2+) were compared between two different astrocyte cell lines, control andρ0astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 andρ0astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2exposure,ρ0astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa2+elevation in control showed higher levels thanρ0at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa2+stress during severe oxidative insult.


1998 ◽  
Vol 46 (9) ◽  
pp. 1272-1278 ◽  
Author(s):  
Q. Li ◽  
P. Ilavarasan ◽  
J.E. Ross ◽  
E.J. Rothwell ◽  
Kun-Mu Chen ◽  
...  

Geophysics ◽  
1986 ◽  
Vol 51 (7) ◽  
pp. 1462-1471 ◽  
Author(s):  
Brian R. Spies ◽  
Dwight E. Eggers

Problems and misunderstandings arise with the concept of apparent resistivity when the analogy between an apparent resistivity computed from geophysical observations and the true resistivity structure of the subsurface is drawn too tightly. Several definitions of apparent resistivity are available for use in electromagnetic methods; however, those most commonly used do not always exhibit the best behavior. Many of the features of the apparent resistivity curve which have been interpreted as physically significant with one definition disappear when alternative definitions are used. It is misleading to compare the detection or resolution capabilities of different field systems or configurations solely on the basis of the apparent resistivity curve. For the in‐loop transient electromagnetic (TEM) method, apparent resistivity computed from the magnetic field response displays much better behavior than that computed from the induced voltage response. A comparison of “exact” and “asymptotic” formulas for the TEM method reveals that automated schemes for distinguishing early‐time and late‐time branches are at best tenuous, and those schemes are doomed to failure for a certain class of resistivity structures (e.g., the loop size is large compared to the layer thickness). For the magnetotelluric (MT) method, apparent resistivity curves defined from the real part of the impedance exhibit much better behavior than curves based on the conventional definition that uses the magnitude of the impedance. Results of using this new definition have characteristics similar to apparent resistivity obtained from time‐domain processing.


1999 ◽  
Vol 2 (03) ◽  
pp. 271-280 ◽  
Author(s):  
Ekrem Kasap ◽  
Kun Huang ◽  
Than Shwe ◽  
Dan Georgi

Summary The formation-rate-analysis (FRASM) technique is introduced. The technique is based on the calculated formation rate by correcting the piston rate with fluid compressibility. A geometric factor is used to account for irregular flow geometry caused by probe drawdown. The technique focuses on the flow from formation, is applicable to both drawdown and buildup data simultaneously, does not require long buildup periods, and can be implemented with a multilinear regression, from which near-wellbore permeability, p * and formation fluid compressibility are readily determined. The field data applications indicate that FRA is much less amenable to data quality because it utilizes the entire data set. Introduction A wireline formation test (WFT) is initiated when a probe from the tool is set against the formation. A measured volume of fluid is then withdrawn from the formation through the probe. The test continues with a buildup period until pressure in the tool reaches formation pressure. WFTs provide formation fluid samples and produce high-precision vertical pressure profiles, which, in turn, can be used to identify formation fluid types and locate fluid contacts. Wireline formation testing is much faster compared with the regular pressure transient testing. Total drawdown time for a formation test is just a few seconds and buildup times vary from less than a second (for permeability of hundreds of millidarcy) to half a minute (for permeability of less than 0.1 md), depending on system volume, drawdown rate, and formation permeability. Because WFT tested volume can be small (a few cubic centimeters), the details of reservoir heterogeneity on a fine scale are given with better spatial resolution than is possible with conventional pressure transient tests. Furthermore, WFTs may be preferable to laboratory core permeability measurements since WFTs are conducted at in-situ reservoir stress and temperature. Various conventional analysis techniques are used in the industry. Spherical-flow analysis utilizes early-time buildup data and usually gives permeability that is within an order of magnitude of the true permeability. For p* determination, cylindrical-flow analysis is preferred because it focuses on late-time buildup data. However, both the cylindrical- and spherical-flow analyses have their drawbacks. Early-time data in spherical-flow analysis results in erroneous p* estimation. Late-time data are obtained after long testing times, especially in low-permeability formations; however, long testing periods are not desirable because of potential tool "sticking" problems. Even after extended testing times, the cylindrical-flow period may not occur or may not be detectable on WFTs. When it does occur, permeability estimates derived from the cylindrical-flow period may be incorrect and their validity is difficult to judge. New concepts and analysis techniques, combined with 3-D numerical studies, have recently been reported in the literature.1–7 Three-dimensional numerical simulation studies1–6 have contributed to the diagnosis of WFT-related problems and the improved analysis of WFT data. The experimental studies7 showed that the geometric factor concept is valid for unsteady state probe pressure tests. This study presents the FRA technique8 that can be applied to the entire WFT where a plot for both drawdown and buildup periods renders straight lines with identical slopes. Numerical simulation studies were used to generate data to test both the conventional and the FRA techniques. The numerical simulation data are ideally suited for such studies because the correct answer is known (e.g., the input data). The new technique and the conventional analysis techniques are also applied to the field data and the results are compared. We first review the theory of conventional analysis techniques, then present the FRA technique for combined drawdown and buildup data. A discussion of the numerical results and the field data applications are followed by the conclusions. Analysis Techniques It has been industry practice to use three conventional techniques, i.e., pseudo-steady-state drawdown (PSSDD), spherical and cylindrical-flow analyses, to calculate permeability and p* Conventional Techniques Pseudo-Steady-State Drawdown (PSSDD). When drawdown data are analyzed, it is assumed that late in the drawdown period the pressure drop stabilizes and the system approaches to a pseudo-steady state when the formation flow rate is equal to the drawdown rate. PSSDD permeability is calculated from Darcy's equation with the stabilized (maximum) pressure drop and the flowrate resulting from the piston withdrawal:9–11 $$k {d}=1754.5\left({q\mu \over r {i}\Delta p {{\rm max}}}\right),\eqno ({\rm 1})$$where kd=PSSDD permeability, md. The other parameters are given in Nomenclature.


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