734 research outputs found

    Cell competition in liver carcinogenesis

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    Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms. While pursuing this goal, it is also effective in selecting against altered/defective cells with putative (pre)-neoplastic potential, thereby edging the risk of cancer development. The flip side of the coin is that the molecular machinery driving cell competition can also be co-opted by neoplastic cell populations to expand unchecked, outside the boundaries of tissue homeostatic control. This review will focus on information that begins to emerge regarding the role of cell competition in liver physiology and pathology. Liver repopulation by normal transplanted hepatocytes is an interesting field of investigation in this regard. The biological coordinates of this process share many features suggesting that cell competition is a driving force for the clearance of endogenous damaged hepatocytes by normal donor-derived cells, as previously proposed. Intriguing analogies between liver repopulation and carcinogenesis will be briefly discussed and the potential dual role of cell competition, as a barrier or a spur to neoplastic development, will be considered. Cell competition is in essence a cooperative strategy organized at tissue level. One facet of such cooperative attitude is expressed in the elimination of altered cells which may represent a threat to the organismal community. On the other hand, the society of cells can be disrupted by the emergence of selfish clones, exploiting the molecular bar codes of cell competition, thereby paving their way to uncontrolled growth

    Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents

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    During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discusse

    Long-term moderate caloric restriction and social isolation synergize to induce anorexia-like behavior in rats

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    Moderate caloric restriction (CR) is an effective strategy to delay the onset of chronic disease states. Conversely, social isolation (SI) carries an increased risk of morbidity and mortality from several causes. The present studies were designed to investigate the long-term effect of the two combined exposures. Two-month-old male rats of the Fischer 344 strain were fed either ad libitum or under a regimen of CR, and each of the two animal sets were housed either in group or isolation. Food consumption and animal growth curves were as expected during the first 6 wk of observation. However, starting at 2 mo and continuing until the fifth month of follow up, rats exposed to both CR and SI showed signs of altered feeding behavior and were unable to complete their (already restricted) meal. Furthermore, altered behavior was accompanied by a corresponding decrease in growth rate until no further increase in body weight was observed. Restoration of group-housing conditions led to a reversal of this phenotype. We conclude that chronic moderate CR and SI synergize to induce anorexia-like behavior, representing a simple and reproducible model to study such an eating disorder

    Infectious agents including COVID-19 and the involvement of blood coagulation and fibrinolysis. A narrative review

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    Platelets, blood coagulation along with fibrinolysis are greatly involved in the pathophysiology of infectious diseases induced by bacteria, parasites and virus. This phenomenon is not surprising since both the innate immunity and the hemostatic systems are two ancestral mechanisms which closely cooperate favoring host's defense against foreign invaders. However, the excessive response of these systems may be dangerous for the host itself

    Clearance of senescent hepatocytes in a neoplastic-prone microenvironment delays the emergence of hepatocellular carcinoma

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    Increasing evidence indicates that carcinogenesis is dependent on the tissue context in which it occurs, implying that the latter can be a target for preventive or therapeutic strategies. We tested the possibility that re-normalizing a senescent, neoplastic-prone tissue microenvironment would exert a modulatory effect on the emergence of neoplastic disease. Rats were exposed to a protocol for the induction of hepatocellular carcinoma (HCC). Using an orthotopic and syngeneic system for cell transplantation, one group of animal was then delivered 8 million normal hepatocytes, via the portal circulation. Hepatocytes transplantation resulted in a prominent decrease in the incidence of both pre-neoplastic and neoplastic lesions. At the end of 1 year 50% of control animals presented with HCC, while no HCC were observed in the transplanted group. Extensive hepatocyte senescence was induced by the carcinogenic protocol in the host liver; however, senescent cells were largely cleared following infusion of normal hepatocytes. Furthermore, levels of Il-6 increased in rats exposed to the carcinogenic protocol, while they returned to near control values in the group receiving hepatocyte transplantation. These results support the concept that strategies aimed at normalizing a neoplastic-prone tissue landscape can modulate progression of neoplastic disease

    Spot size measurements in the Eli-NP compton gamma source

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    A high brightness electron Linac is being built in the Compton Gamma Source at the ELI Nuclear Physics facility in Romania. To achieve the design luminosity, a train of 32 bunches with a nominal charge of 250 pC and 16 ns spacing , will collide with the laser beam in the interaction point. Electron beam spot size is measured with an OTR (optical transition radiation) profile moni-tors. In order to measure the beam properties, the optical radiation detecting system must have the necessary accu-racy and resolution. This paper deals with the studies of different optic configurations to achieve the magnifica-tion, resolution and accuracy desired considering design and technological constraints; we will compare several configurations of the optical detection line to justify the one chosen for the implementation in the Lina

    Human immunodeficiency virus type 2 (HIV-2) Gag is trafficked in an AP-3 and AP-5 dependent manner

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    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release

    Time-restricted feeding delays the emergence of the age-associated, neoplastic-prone tissue landscape

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    Aging increases the risk of cancer partly through alterations in the tissue microenvironment. Time-restricted feeding (TRF) is being proposed as an effective strategy to delay biological aging. In the present studies, we assessed the effect of long-term exposure to TRF on the emergence of the age-associated, neoplastic-prone tissue landscape. Animals were exposed to either ad libitum feeding (ALF) or TRF for 18 months and then transplanted with hepatocytes isolated from pre-neoplastic nodules. Both groups were continued ALF and the growth of transplanted cells was evaluated 3 months later. A significant decrease in frequency of larger size clusters of pre-neoplastic hepatocytes was seen in TRF-exposed group compared to controls. Furthermore, TRF modified several parameters related to both liver and systemic aging towards the persistence of a younger phenotype, including a decrease in liver cell senescence, diminished fat accumulation and up-regulation of SIRT1 in the liver, down-regulation of plasma IGF-1, decreased levels of plasma lipoproteins and up-regulation of hippocampal brain-derived growth factor (BDNF).These results indicate that TRF was able to delay the onset of the neoplastic-prone tissue landscape typical of aging. To our knowledge, this is the first investigation to describe a direct beneficial effect of TRF on early phases of carcinogenesis

    A Method of Synthesis for Multi-Frequency Smart Antenna Arrays for Coastal Monitoring

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    Thanks to their versatility, smart antenna arrays are used in a wide variety of contexts, including, in particular, coastal monitoring. Within this framework, operating in multi-frequency modality might reveal a fundamental requirement. So, in this paper the problem of synthesis of multi-frequency antenna arrays is addressed. Precisely, a fixed grid array is considered, having an arbitrary but known geometry. The excitation vectors are optimized in such a way that the radiation patterns belong to a prescribed mask at certain assigned frequencies. Moreover, in order to have a simpler, cheaper and more efficient antenna, the phase-only synthesis is performed. In fact, thanks to this requirement, variable attenuators are not necessary and only phase-shifters are used in the feeding network. Numerical examples are provided, which validate the effectiveness of the method
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