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Intestinal inflammation is associated with low levels of mucosal ATP, highlighting the importance of mitochondrial function associated with ATP production in the pathophysiology of the disease. In the inflamed colon of humans and mice, we found decreased levels of mitochondrial complex cytochrome c oxidase I/IV and lower ATP levels. Thus, we generated colonic ρ0 cells with reduced mitochondrial function linked to ATP production by selective depletion of mitochondrial DNA. In these cells, RNA sequencing revealed a substantial number of differentially expressed transcripts, among which 240 belonged to inflammatory pathways activated in human inflamed colon and TNF-α-treated cells (false discovery rate < 0.05). TNF-α treatment of colonic ρ0 cells augmented IL-8 expression by 9-fold (P < 0.01) via NF-κB compared to TNF-α-treated control. Moreover, reduced mitochondrial function facilitated TNF-α-mediated NF-κB luciferase promoter activity as a result of lowered inhibitory IκBα (nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor, α), leading to elevated NF-κB. In cells with reduced mitochondrial function, TNF-α facilitated AMPKα2 activation by 8-fold (P < 0.01), which was involved in NF-κB-dependent IL-8 expression. Last, in human and mouse colon, anti-TNF-α treatment restored reduced mitochondria-dependent inflammation. We propose that selective targeting of this novel mechanism provides new treatment opportunities for intestinal inflammation.—Heller, S., Penrose, H. M., Cable, C., Biswas, D., Nakhoul, H., Baddoo, M., Flemington, E., Crawford, S. E., Savkovic, S. D. Reduced mitochondrial activity in colonocytes facilitates AMPKα2-dependent inflammation.

Bandicoot rat, Bandicota bengalensis, received intraperitoneal inoculation of Trypanosoma (Trypanozoon) evansi flagellates and showed acute disease, leading to death during the 2nd peak of parasitaemia [14th day post infection (pi)]. Damage in brain and choroid plexus of the infected bandicoot is studied on the 5th, 8th, 12th and 14th day post inoculation. Sign of histopathological changes in the brain and choroid plexus of the bandicoot are detected after 1st peak of parasitaemia. Infiltration of lymphocyte and plasma cells, congestion, perivascular cuffing, gliosis and brain lesions are observed during 12th–14th day post intection. Multiple sclerosis, neuronophagia, focal haemorrhage, cerebral hyperplasia, oligodendrocytoma, astrocytoma and fatty degeneration of brain tissue are also found. Alteration in the ependymal cells of choroid plexus is noticed. Extensive oedema, infiltration of inflammatory cells and rupture of ventricular ependymal layer are found. Parasites are found both in the brain tissue and choroid plexus. No intracellular stage of the parasite is observed. The nature of damage in the brain tissue and choroid plexus shows similarity with the cases of African trypanosomiasis. This salivarian species cause more deleterious effect in brain much earlier in the disease course than its African relatives.

Intestinal inflammation has been recently characterized by the dysregulation of lipids as metabolic and energy sources, revealing a novel feature of its pathophysiology. Because intracellular lipids, stored in dynamic lipid droplets (LDs), provide energy for cellular needs, we investigated whether they play a role in intestinal inflammation. In the inflamed intestine of mice, elevated LDs were found in colonic and infiltrating immune cells as shown by staining for the LD coat protein PLIN2 and for lipids with BODIPY. In colonic cells, TNF stimulated LD increases by receptor signaling rely on phosphatidylinositol 3-kinase activation. Downstream, TNF triggered a negative regulatory loop between LDs and the transcription factor FOXO3. This was shown in the colon of Foxo3-deficient mice, where elevation in PLIN2 and lipids were further facilitated by inflammation and were more prominent relative to wild-type, whereas, in colonic cells, inhibition of lipogenesis blocked the TNF-mediated loss of FOXO3. Furthermore, blockade of PGE2 synthesis abrogated TNF-stimulated increases in LDs and FOXO3 inactivation. We found in colonic tissue of Foxo3-deficient mice higher levels of cyclooxygenase-2, a mediator of prostaglandin E2 (PGE2) synthesis, supporting involvement of PGE2 in the LD-FOXO3 regulatory loop. Ultimately, TNF-stimulated lipogenesis leading to elevated LDs facilitated NF-κB-mediated increases in IL-8 protein, which is associated with the surface of LDs found in the lumina of the endoplasmic reticulum and Golgi apparatus. This novel immunometabolic mechanism of colonic inflammation involving elevated LDs could provide opportunities for new treatment options.

In order for structured light methods to work outside, the strong background from the sun needs to be suppressed. This can be done with bandpass filters, fast shutters, and background subtraction. In general this last method necessitates the sensor system to be stationary during data taking. The contribution of this paper is a method to compensate for the motion if the system is moving. The key idea is to use video stabilization techniques that work even if the illuminator is switched on and off from one frame to another. We used OpenCV functions and modules to implement a robust and efficient method. We evaluated it under various conditions and tested it on a moving robot outdoors. We will demonstrate that one can not only do 3D reconstruction under strong ambient light, but that it is also possible to observe optical properties of the objects in the environment.

Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity,'' causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr(-/-) mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented. WD-induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells led to increased proliferation and enhanced innate immune responses. Quantitative trait locus (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome-mediated trained immunity. Consistently, Nlrp3(-/-)/Ldlr(-/-) mice lacked WD-induced systemic inflammation, myeloidprogenitor proliferation, and re-programming. Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.

Experimental infection of Trypanosoma (Trypanozoon) evansi in Bandicota bengalensis produces an acute disease course leading to untimely death of the bandicoot rat. The sequential alteration of liver, spleen, lung, kidney, and heart was studied on the 5th, 8th, 12th, and 14th days postinoculation. The rats showed inflammatory, degenerative, and necrotic changes in these organs. In liver, pseudolobule formation, necrosis and hemorrhage within the sinusoids, and fatty degeneration of hepatic cells were the predominant histopathological changes. The changes were destructive and irreversible. In spleen giant cells aggregation and granulomatous lesion, i.e., accumulation of histiocytes, were the protective changes, whereas tissue and cell damage indicated irreversible degeneration. The gradual development of intrabronchus inflammation, aggregation of inflammatory cells around the alveoli, congestion of bronchioles, septal edema, atrophy of alveolar walls, migration of macrophages, and emphysema were the histopathological changes noticed in the lungs of the infected rats. The affected kidney showed infiltration of lymphocytes, hemorrhage in the interlobular space, and glomerulitis as the irreversible and destructive changes in the rats. There was degeneration of myocardium in the hearts of the rats. The histopathological changes in these organs are compared with those studied in surra, human sleeping sickness disease, and African trypanosomiasis. Possible mechanisms for these histological changes in the visceral organs are discussed.