scholarly journals Ovarian Cancer Dissemination—A Cell Biologist’s Perspective

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1957 ◽  
Author(s):  
Sadaf Farsinejad ◽  
Thomas Cattabiani ◽  
Taru Muranen ◽  
Marcin Iwanicki

Epithelial ovarian cancer (EOC) comprises multiple disease states representing a variety of distinct tumors that, irrespective of tissue of origin, genetic aberrations and pathological features, share common patterns of dissemination to the peritoneal cavity. EOC peritoneal dissemination is a stepwise process that includes the formation of malignant outgrowths that detach and establish widespread peritoneal metastases through adhesion to serosal membranes. The cell biology associated with outgrowth formation, detachment, and de novo adhesion is at the nexus of diverse genetic backgrounds that characterize the disease. Development of treatment for metastatic disease will require detailed characterization of cellular processes involved in each step of EOC peritoneal dissemination. This article offers a review of the literature that relates to the current stage of knowledge about distinct steps of EOC peritoneal dissemination, with emphasis on the cell biology aspects of the process.

2010 ◽  
Vol 1274 ◽  
Author(s):  
David Taylor ◽  
Lauren Mulcahy ◽  
Gerardo Presbitero ◽  
Pietro Tisbo ◽  
Clodagh Dooley ◽  
...  

AbstractWe have proposed a new model for microcrack detection by osteocytes in bone. According to this model, cell signalling is initiated by the cutting of cellular processes which span the crack. We show that shear displacements of the crack faces are needed to rupture these processes, in an action similar to that of a pair of scissors. Current work involves a combination of cell biology experiments, theoretical and experimental fracture mechanics and system modelling using control theory approaches. The approach will be useful for understanding effects of extreme loading, aging, disease states and drug treatments on bone damage and repair; the present paper presents recent results from experiments and simulations as part of current, ongoing research.


2004 ◽  
Vol 72 (5) ◽  
pp. 2964-2975 ◽  
Author(s):  
Elizabeth A. Joyce ◽  
Amita Kawale ◽  
Stefano Censini ◽  
Charles C. Kim ◽  
Antonello Covacci ◽  
...  

ABSTRACT Streptococcus pneumoniae causes several diseases, including otitis media, pneumonia, and meningitis. Although little is known about the regulation of or how individual pneumococcal factors contribute to these disease states, there is evidence suggesting that some factors are regulated by a cell-density-dependent mechanism (quorum sensing). Quorum sensing allows bacteria to couple transcription with changes in cell density; bacteria achieve this by sensing and responding to small diffusible signaling molecules. We investigated how the LuxS signaling system impacts the biology of S. pneumoniae. An analysis of the transcriptional profiles of a serotype 2 strain and an isogenic luxS deletion strain utilizing an S. pneumoniae-specific microarray indicated that LuxS regulates gene expression involved in discrete cellular processes, including pneumolysin expression. Contrary to the paradigm for quorum sensing, we observed pronounced effects on transcription in early log phase, where gene expression was repressed in the mutant. Assessing the mutant for its ability to infect and cause disease in animals revealed a profound defect in ability to persist in the nasopharyngeal tissues. Our analysis of an S. pneumoniae transcriptome revealed a function for LuxS in gene regulation that is not dependent upon high cell density and is likely involved in the maintenance of pneumococcal load in susceptible hosts.


1979 ◽  
Author(s):  
C.J.W. van Ginkel ◽  
J.A. van Mourik ◽  
J.I.H. Oh ◽  
J. Vreeken ◽  
W.U. van Aken

During short-terra culture monocytes (M) only, not granulocytes or lymphocytes, generate thromboplastin (TP) activity which is absent Immediately after isolation. To clarify the mechanism whereby M generate TP, J approaches were applied: I. To investigate the presence of hidden” TP, freshly Isolated M were subjected either to mechanical disruption, to enzymatic stripping or to dellpldation, followed by reconstitution of the lipoproteins with exogenous phospholipids. No TP activity could be detected after any of these treatments. II. Using an antiserum against human brain TP apoprotein which cross-reacted with monocyte TP, it was shown that intact and disrupted freshly Isolated M lack TP related antigen whereas cultured M display binding of anti-TP antibodies. However, M cultured in the presence of protein synthesis Inhibitors and cultured lymphocytes, lacked TP antigen. III. Using several agents known to affect cellular processes, TP generation was shown to be dependent on;protein and RNA synthesis, energy metabolism, cAMP metabolism, assemblage of microtubules and divalent cations. Inhibition of prostaglandin synthesis by indomethacln did not arrect TP generation. M from 3 patients with COD displayed normal TP generation. These two observations suggest that prostaglandin synthesis and oxygen radicals are not involved Is TP generation. In conelusion, our data indicates that de novo synthesis of TP apoprotein Is responsible for the in vitro generation of TP activity by monocytes.


2021 ◽  
Vol 22 (18) ◽  
pp. 9945
Author(s):  
Luisa Galla ◽  
Nicola Vajente ◽  
Diana Pendin ◽  
Paola Pizzo ◽  
Tullio Pozzan ◽  
...  

Calcium (Ca2+) exerts a pivotal role in controlling both physiological and detrimental cellular processes. This versatility is due to the existence of a cell-specific molecular Ca2+ toolkit and its fine subcellular compartmentalization. Study of the role of Ca2+ in cellular physiopathology greatly benefits from tools capable of quantitatively measuring its dynamic concentration ([Ca2+]) simultaneously within organelles and in the cytosol to correlate localized and global [Ca2+] changes. To this aim, as nucleoplasm Ca2+ changes mirror those of the cytosol, we generated a novel nuclear-targeted version of a Föster resonance energy transfer (FRET)-based Ca2+ probe. In particular, we modified the previously described nuclear Ca2+ sensor, H2BD3cpv, by substituting the donor ECFP with mCerulean3, a brighter and more photostable fluorescent protein. The thorough characterization of this sensor in HeLa cells demonstrated that it significantly improved the brightness and photostability compared to the original probe, thus obtaining a probe suitable for more accurate quantitative Ca2+ measurements. The affinity for Ca2+ was determined in situ. Finally, we successfully applied the new probe to confirm that cytoplasmic and nucleoplasmic Ca2+ levels were similar in both resting conditions and upon cell stimulation. Examples of simultaneous monitoring of Ca2+ signal dynamics in different subcellular compartments in the very same cells are also presented.


2021 ◽  
Author(s):  
Rebecca K. Donegan ◽  
Jacqueline Copeland ◽  
Stanzin Edgha ◽  
Gabriel Brown ◽  
Owen F. Hale ◽  
...  

Heme is both an essential cofactor and an abundant source of nutritional iron for the human pathogen Mycobacterium tuberculosis (Mtb). While heme is required for Mtb survival and virulence, it is also potentially cytotoxic. Since Mtb has the ability to both make and uptake heme, the de novo synthesis of heme and its acquisition from the host must be balanced in order to mitigate heme toxicity. However, the mechanisms employed by Mtb to regulate heme uptake, synthesis, and bioavailability are poorly understood. By integrating ratiometric heme sensors with mycobacterial genetics, cell biology, and biochemistry, we determined that the terminal heme biosynthetic enzyme, coproheme decarboxylase (ChdC), plays a role in regulating both heme bioavailability and uptake in Mtb. Moreover, we found that Mtb has a preference for scavenging reduced ferrous heme and exhibits a cell surface heme reductase activity that is regulated by ChdC. In Mtb, ChdC expression is down-regulated when iron is limiting, which in-turn increases both heme import and bioavailability. Such a mechanism may serve to protect cells from heme toxicity while trying to meet the nutritional demand for iron. Our results demonstrate that heme synthesis and uptake are tightly integrated in mycobacteria and represent the first example of a heme synthetic enzyme playing a role in controlling heme uptake.


Botany ◽  
2014 ◽  
Vol 92 (7) ◽  
pp. 495-511 ◽  
Author(s):  
Rodney Arthur Savidge

A mature bordered pit in secondary xylem of Pinaceae comprises a circular border of secondary-wall material that protrudes into the tracheid lumen and is punctuated by a centralized aperture through which sap flows. The overarching border encloses a pit chamber within which is a “membrane”, or diaphragm, consisting of a central torus and margo strands. Bordered-pit pairs are abundantly present in all woods, and their membranes serve as swinging-diaphragm check valves regulating sap flow between adjoining tracheary elements, simultaneously trapping emboli and particulates in water as it moves from roots to leaves. The cell biology of bordered-pit formation in cambial derivatives of Abies balsamea (L.) Mill. was investigated by light and scanning electron microscopy during early stages of cellular differentiation of cambial derivatives into secondary xylem tracheids. A bordered-pit template (BPT), a bordered-pit organelle (BPO), a bordered-pit basal disk, and additional novel structures were found to be associated with bordered-pit formation. Evidence was found that the membrane does not comprise residual compound middle lamella; rather, the membrane forms de novo as BPO remnants. A cell-biology model and new terminology are introduced to explain how BPTs, BPOs, and basal disks contribute to successive stages in formation of bordered-pit pairs.


1979 ◽  
Author(s):  
C van Ginkel ◽  
J van Mourik ◽  
J Vreeken ◽  
W van Aken

During short-term culture monocytes (M) only, not granulocytes or lymphocytes, generate thromboplastin (TP) activity which is absent immediately after isolation. To clarify the mechanism whereby M generate TP,3 approaches were applied; I.To investigate the presence of hidden TP,freshly isolated M were subjected either to mechanical disruption, to enzymatic stripping or to delipidation, followed by reconstitution of the lipoproteins with exogenous phospholipids. No TP activity could be detected after any of these treatments. II. Using an antiserum against human brain TP apoprotein which cross-reacted with monocyte TP, it was shown that intact and disrupted freshly isolated M lack TP related antigen whereas cultured M display binding of anti-TP antibodies. However, M cultured in the presence of protein synthesis inhibitors and cultured lymphocytes, lacked TP antigen.III. Using several agents known to affect cellular processes,TP generation was shown to be dependent on:protein and RNA synthesis,energy metabolism,cAMP metabolism,assemblage of microtubules and divalent cations. Inhibition of prostaglandin synthesis by indomethacin did not affect TP generation. M from 3 patients with CGD displayed normal TP generation. These two observations suggest that prostaglandin synthesis and oxygen radicals are not involved in TP generation. In conclusion,our data indicates that de novo synthesis of TP apoprotein is responsible for the in vitro generation of TP activity by monocytes.


PLoS Biology ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. e3001277
Author(s):  
Stefan Schulze ◽  
Friedhelm Pfeiffer ◽  
Benjamin A. Garcia ◽  
Mechthild Pohlschroder

Glycosylation is one of the most complex posttranslational protein modifications. Its importance has been established not only for eukaryotes but also for a variety of prokaryotic cellular processes, such as biofilm formation, motility, and mating. However, comprehensive glycoproteomic analyses are largely missing in prokaryotes. Here, we extend the phenotypic characterization of N-glycosylation pathway mutants in Haloferax volcanii and provide a detailed glycoproteome for this model archaeon through the mass spectrometric analysis of intact glycopeptides. Using in-depth glycoproteomic datasets generated for the wild-type (WT) and mutant strains as well as a reanalysis of datasets within the Archaeal Proteome Project (ArcPP), we identify the largest archaeal glycoproteome described so far. We further show that different N-glycosylation pathways can modify the same glycosites under the same culture conditions. The extent and complexity of the Hfx. volcanii N-glycoproteome revealed here provide new insights into the roles of N-glycosylation in archaeal cell biology.


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