Identified central neurons convey a mitogenic signal from a peripheral target to the CNS

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2331-2337 ◽  
Author(s):  
T.S. Becker ◽  
G. Bothe ◽  
A.J. Berliner ◽  
E.R. Macagno
Keyword(s):  
Cell Proliferation ◽  
Ventral Nerve Cord ◽  
The Other ◽  
Detectable Effect ◽  
Peripheral Target ◽  
Compensatory Response ◽  
Central Neurons ◽  
Efferent Projections ◽  
Inductive Signal ◽  
Mitogenic Signal

Regulation of central neurogenesis by a peripheral target has been previously demonstrated in the ventral nerve cord of the leech Hirudo medicinalis (Baptista, C. A., Gershon, T. R. and Macagno, E. R. (1990). Nature 346, 855–858) Specifically, innervation of the male genitalia by the fifth and sixth segmental ganglia (the sex ganglia) was shown to trigger the birth of several hundred central neurons (PIC neurons) in these ganglia. As reported here, removal of the target early during induction shows that PIC neurons can be independently induced in each side of a ganglion, indicating that the inductive signal is both highly localized and conveyed to each hemiganglion independently. Further, since recent observations (Becker, T., Berliner, A. J., Nitabach, M. N., Gan, W.-B. and Macagno, E. R. (1995). Development, 121, 359–369) had indicated that efferent projections are probably involved in this phenomenon, we individually ablated all possible candidates, which led to the identification of two central neurons that appear to play significant roles in conveying the inductive signal to the CNS. Ablation of a single ML neuron reduced cell proliferation in its own hemiganglion by nearly 50%, on the average. In contrast, proliferation on the opposite side of the ganglion increased by about 25%, suggesting the possibility of a compensatory response by the remaining contralateral ML neuron. Simultaneous ablation of both ML neurons in a sex ganglion caused similar reductions in cell proliferation in each hemiganglion. Deletion of a single AL neuron produced a weaker (7%) but nonetheless reproducible reduction. Ablation of the other nine central neurons that might have been involved in PIC neuron induction had no detectable effect. Both ML and AL neurons exhibit ipsilateral peripheral projections, and both arborize mostly in the hemiganglion where they reside. Thus, we conclude that peripheral regulation of central neurogenesis is mediated in the leech by inductive signals conveyed retrogradely to each hemiganglion by specific central neurons that innervate this target and the hemiganglion they affect.

Target-induced neurogenesis in the leech CNS involves efferent projections to the target

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 359-369 ◽  
Author(s):  
T. Becker ◽  
A.J. Berliner ◽  
M.N. Nitabach ◽  
W.B. Gan ◽  
E.R. Macagno
Keyword(s):  
Sensory Neurons ◽  
Male Genitalia ◽  
Critical Period ◽  
Neuronal Cells ◽  
Sexual Organ ◽  
Central Neurons ◽  
Efferent Projections ◽  
Male Organ ◽  
Peripheral Sensory ◽  
Inductive Signal

During a critical period in leech embryogenesis, the sex nerves that connect the 5th and 6th midbody ganglia (MG5 and MG6) to the primordium of the male sexual organ carry a spatially localized signal that induces the birth of several hundred neurons specific to these ganglia. We examined particular cellular elements (afferents, efferents, non-neuronal components) within these nerves as potential conveyors of the inductive signal. We show that axons of peripheral sensory neurons in the male genitalia travel along the sex nerves and into MG5 and MG6, but reach the CNS after the critical period has elapsed and cannot, therefore, be involved in the induction. Of the six sex nerves, four contain non-neuronal cells that span the entire distance between the male genitalia and the sex ganglia. However, when male genitalia were transplanted to ectopic locations close to MG6, induction occurred frequently but only in MG6, mediated by ectopic nerves that do not contain these cells. Thus, non-neuronal cells specific to the normal sex nerves are not necessary for induction. In addition, dye injections into the target during the critical period failed to reveal migrating cells in the sex nerves that could convey the inductive signal to the CNS. Finally, we show that 11 pairs of central neurons in each ganglion project to the male organ early during the critical period. In the adult, at least 3 additional pairs of neurons in MG6 also innervate this target. We conclude that the only components of the sex nerves that connect the sex ganglia to the target during the critical period that could be associated with induced central mitogenesis are the axons of central neurons that innervate the male genitalia.

scholarly journals Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 181
Author(s):  
Francesca Zonta ◽  
Christian Borgo ◽  
Camila Paz Quezada Meza ◽  
Ionica Masgras ◽  
Andrea Rasola ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Therapeutic Strategies ◽  
The Other ◽  
Osteosarcoma Cell ◽  
Monomeric Form ◽  
New Information

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.

An evolutionary and developmental approach toward understanding of growth variations of two closely related dwarfism of Galium verum

Biologia ◽  
2014 ◽  
Vol 69 (12) ◽  
Author(s):  
Keum Jeong ◽  
Jae-Hong Pak ◽  
Jeong Kim
Keyword(s):  
Cell Proliferation ◽  
Genetic Factors ◽  
Expression Patterns ◽  
Mrna Differential Display ◽  
Growth Patterns ◽  
The Other ◽  
Differential Growth ◽  
Developmental Approach ◽  
Differential Display Method ◽  
Low Activity

AbstractGalium L. is one of the largest and most widespread genus of Rubiaceae, consisting of more than 650 species worldwide. Galium verum var. asiaticum (G. verum a.) is a perennial herbaceous and widely distributed in in Korea peninsula. On the other hand, Galium verum var. asiaticum for. pusillum (G. verum a.p.) is endemic to Korea, inhabiting only on high land of Mt. Halla of Jeju. G. verum a.p. appears to be a dwarfism of G. verum a. We wondered what physiological, environmental, or genetic factors rendered those two taxa morphologically differentiated. We found that G. verum a.p. shows a low activity of the cell proliferation and was not associated with responsiveness contents of auxin and gibberellins. In order to search for genetic factors involved, we carried out an mRNA differential display method using the ACPs, and isolated several different expression genes between the two taxa. We chose one of those genes, which encoded RADIALIS-like proteins: GvaRADL1 from G. verum a. and GvapRADL1 from G. verum a.p. We discuss the relevancy of the genetic variations in regard to the differential expression patterns of those genes and the differential growth patterns of the two variants.

scholarly journals Glomerulonephritis in schistosomiasis with mesangial IgM deposits

1981 ◽  
Vol 76 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Ageu Godoy Magalhães Filho ◽  
Antônio Victoriano Barbosa ◽  
Teresa Cristina Ferreira
Keyword(s):  
Cell Proliferation ◽  
Light Microscopy ◽  
Immunofluorescence Microscopy ◽  
The Other ◽  
Proliferative Glomerulonephritis ◽  
Mesangial Proliferative Glomerulonephritis ◽  
Normal Pattern ◽  
Glomerular Lesions ◽  
Capillary Walls ◽  
Igm Deposits

Twenty one cases of hepatoesplenic schistosomiasis patients without clinical and laboratory evidence of renal disease, were studied by surgical biopsies using light microscopy and immunofluorescence. The cases were classified histologically as: normal pattern (6 cases); minimal changes (6 cases); and mesangial proliferative glomerulonephritis (9 cases). By the immunofluorescence microscopy using anti IgM, IgG, IgA and C3, the predominant finding in all biopsies, except the normal cases, was granular deposits of IgM in the mesangium along with C3. On the other hand, IgG was present in all cases including normal biopsies along the capillary walls. However IgG was also present in the mesangium only in cases with glomerular lesions. This finding may well be similar to that recently described as IgM mesangial nephropathy. According to our cases a mesangial proliferative glomerulonephritis, characterized by segmental cell proliferation and deposition of IgM in the mesangium, is probably the entity found in the early stages of mansonic schistosomiasis.

Benzamide on chondrocytic differentiation in chick limb bud cell culture

Development ◽  
1985 ◽  
Vol 85 (1) ◽  
pp. 163-175
Author(s):  
Shinobu Nakanishi ◽  
Edwin M. Uyeki
Keyword(s):  
Cell Culture ◽  
Cell Proliferation ◽  
Trichloroacetic Acid ◽  
Rna Synthesis ◽  
Limb Bud ◽  
The Other ◽  
Transferase Activity ◽  
Dna And Rna ◽  
Atp Levels ◽  
Chondrocytic Differentiation

Benzamide, an inhibitor of (ADP-ribose) transferase, augmented chondrocytic differentiation of chick limb bud mesenchymal cells in micromass cultures; the incorporation of 35SO42− into the trichloroacetic-acid-insoluble constituents of cell masses as well as the formation of cartilage nodules (Nishio, Nakanishi, Doull & Uyeki, 1983) occurred about 24h earlier than in untreated cultures and continued to be enhanced in benzamide-treated cultures of stage 23- to 24-chick limb bud cells. Benzamide also significantly increased cell proliferation. However, benzamide did not affect DNA and RNA syntheses except for one period: 24 to 30 h after the start of culture, RNA synthesis was stimulated. From 48h of culture, (ADP-ribose) transferase activity decreased daily in untreated cultures, whereas benzamide treatment diminished (ADP-ribose) transferase activity 24 h earlier. On the other hand, intracellular NAD levels increased daily in untreated cultures, and benzamide significantly increased the NAD levels above untreated cultures. ATP levels did not differ significantly during the culture period, and benzamide did not affect ATP levels.

O-linked but not N-linked glycosylation is necessary for the secretion of endoglucanases I and II by Trichoderma reesei

1987 ◽  
Vol 33 (8) ◽  
pp. 698-703 ◽  
Author(s):  
C. P. Kubicek ◽  
T. Panda ◽  
G. Schreferl-kunar ◽  
F. Gruber ◽  
R. Messner
Keyword(s):  
Trichoderma Reesei ◽  
Protein Glycosylation ◽  
The Other ◽  
Detectable Effect ◽  
Secreted Protein ◽  
Intracellular Protein ◽  
Molecular Weights ◽  
Sds Page ◽  
Wide Range ◽  
Molecular Masses

The effect of inhibiting protein glycosylation was studied in nongrowing mycelia and protoplasts of Trichoderma reesei which secreted two endoglucanases (I and II) upon addition of sophorose. Tunicamycin (40 μg∙mL−1) inhibited incorporation of N-acetylglucosamine into secreted protein, but had no effect on secretion of total protein or endoglucanases. The secreted endoglucanases I and II exhibited relative molecular masses of 58 and 45 kilodaltons, respectively, irrespective of the presence of tunicamycin. On the other hand 2-deoxy-D-glucose inhibited the biosynthesis of extracellular as well as intracellular protein over a wide range of concentrations; at 50 μg∙mL−1, however, it inhibited the synthesis of extracellular protein more strongly. The synthesis of endoglucanases I and II was decreased accordingly under these conditions. SDS–PAGE did not reveal the secretion of endoglucanases with smaller molecular weights. When the two endoglucanases were purified and subjected to Endo H treatment or β-elimination, the former had no detectable effect, whereas the latter released all carbohydrate from the protein. Nevertheless, endoglucanases I and II contained 1.3 and 0.5 mol of glucosamine per mol enzyme, respectively. It is concluded that endoglucanases I and II from T. reesei contain mainly O-linked neutral carbohydrate, which is required for their secretion.

scholarly journals Cerebellar granule cells contain a membrane mitogen for cultured Schwann cells.

1989 ◽  
Vol 108 (2) ◽  
pp. 607-611 ◽  
Author(s):  
P W Mason ◽  
J W Bigbee ◽  
G H DeVries
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cultures ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Proteoglycan Synthesis ◽  
Cerebellar Granule ◽  
Mitogenic Signal

Proliferation of Schwann cells is one of the first events that occurs after contact with a growing axon. To further define the distribution and properties of this axonal mitogen, we have (a) cocultured cerebellar granule cells, which lack glial ensheathment in vivo with Schwann cells; and (b) exposed Schwann cell cultures to isolated granule cell membranes. Schwann cells cocultured with granule cells had a 30-fold increase in the labeling index over Schwann cells cultured alone, suggesting that the mitogen is located on the granule cell surface. Inhibition of granule cell proteoglycan synthesis caused a decrease in the granule cells' ability to stimulate Schwann cell proliferation. Membranes isolated from cerebellar granule cells when added to Schwann cell cultures caused a 45-fold stimulation in [3H]thymidine incorporation. The granule cell mitogenic signal was heat and trypsin sensitive and did not require lysosomal processing by Schwann cells to elicit its proliferative effect. The ability of granule cells and their isolated membranes to stimulate Schwann cell proliferation suggests that the mitogenic signal for Schwann cells is a ubiquitous factor present on all axons regardless of their ultimate state of glial ensheathment.

Histologic Findings in Persistent Hyperinsulinemic Hypoglycemia of Infancy: Australian Experience

2000 ◽  
Vol 3 (6) ◽  
pp. 532-547 ◽  
Author(s):  
Michelle M. Jack ◽  
Rosslyn M. Walker ◽  
Michael J. Thomsett ◽  
Andrew M. Cotterill ◽  
John R. Bell
Keyword(s):  
Cell Proliferation ◽  
Normal Subjects ◽  
Pancreatic Tissue ◽  
The Other ◽  
Controlled Study ◽  
Cytokeratin 19 ◽  
Hyperinsulinemic Hypoglycemia ◽  
Cell Nuclei ◽  
Β Cell ◽  
Diffuse Disease

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by hyperinsulinism and profound hypoglycemia, with most children requiring pancreatic resection. The histological classification of PHHI is controversial. Most authors acknowledge the existence of focal areas of islet cell proliferation (adenomatosis) in 30%–50% of cases and a diffuse disorganisation of islet architecture, termed “nesidiodysplasia,” in others. De Lonlay et al. reported that cases with adenomatosis are focal with normal remainder of pancreas and that focal and diffuse disease can be differentiated intraoperatively, on the basis of increased β-cell nuclear size found only in the diffusely abnormal pancreas. We have examined pancreatic histology in a blinded controlled study of PHHI patients. Pancreatic tissue was obtained at autopsy from 60 normal subjects (age 17 weeks gestation to 76 years) and from surgical specimens of 31 PHHI patients. Sections from PHHI subjects ( n = 294 blocks) and control sections were stained with hematoxylin and eosin, insulin, glucagon, somatostatin, NSE, cytokeratin 19, and vimentin. Three sections from each PHHI patient were randomly chosen for further analysis. Age-matched control ( n = 34) and PHHI sections ( n = 66) were examined, with the identity of subjects concealed. A diagnosis of normal histology, adenomatosis, or diffuse nesidiodysplasia was recorded for each section. The presence of large β-cell nuclei (>19 μm), ductuloinsular complexes, and centroacinar cell proliferation was noted. Of a total of 65 subjects examined (34 control and 31 PHHI), 37 subjects were identified as normal on both sections examined. All the control cases were correctly identified as normal and none had large β-cell nuclei or centroacinar cell proliferation. Of 31 PHHI patients, 28 were identified as abnormal, either on the basis of abnormal architecture and/or abnormally large β-cell nuclei. Three patients were identified as normal in both sections. Fifteen of 31 patients had diffuse nesidiodysplasia only. Of 13 patients with areas of adenomatosis, 2 had resection of a nodule with adenomatosis present in most of the tissue removed at surgery. Nine patients had a diagnosis of adenomatosis in one section and a diagnosis of diffuse nesidiodysplasia in the other sections from nonadjacent pancreas. Only 2 of 31 PHHI cases had adenomatosis on one section examined and normal pancreas on the other section examined. Large β-cell nuclei were variably found in PHHI sections. Only 5 of 15 patients with diffuse nesidiodysplasia had large nuclei in both sections examined. Centroacinar cell proliferation was identified in 12 PHHI subjects, 6 with adenomatosis and diffuse nesidiodysplasia and 6 with diffuse changes only. It was patchy in distribution within sections and present in only one section in 7 of the 12 subjects. In summary, we have shown that a blinded observer could differentiate control and PHHI pancreatic tissue. Only 2 of 31 patients (6%) had focal adenomatosis with normal nonadjacent pancreas, the majority (24 of 31) had diffuse nesidiodysplasia affecting the remainder of their pancreas, with 38% (9 of 24) also having areas of adenomatosis. Large β-cell nuclei did not reliably identify those with diffuse disease in this study. There was evidence of significant ductal and centroacinar proliferation in 39% of PHHI cases, which was not observed in any of the controls. We have shown that PHHI subjects have a spectrum of pancreatic histological abnormalities, from no abnormality to diffuse subtle changes to florid adenomatosis. Patients could not be segregated into subtypes for different operative intervention despite the availability of full immunohistochemical staining.

scholarly journals IL-33/IL-31 Axis: A Potential Inflammatory Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Eleonora Di Salvo ◽  
Elvira Ventura-Spagnolo ◽  
Marco Casciaro ◽  
Michele Navarra ◽  
Sebastiano Gangemi
Keyword(s):  
Cell Proliferation ◽  
Immune System ◽  
Literature Review ◽  
Inflammatory Process ◽  
The Other ◽  
Human Tissues ◽  
Biological Functions ◽  
Huge Amount ◽  
Tissue Remodelling ◽  
Near Future

Cytokines play an important role in the regulation of the immune system (adaptive and innate). Given their importance in proinflammatory processes, cytokines have been used for understanding the pathogenesis and as biomarkers in many diseases. IL-31 and IL-33 are still considered novel cytokines. IL-31 controls signalling and regulates a huge amount of biological functions: it induces proinflammatory cytokines, regulates cell proliferation, and is involved also in tissue remodelling. On the other hand, IL-33 has been identified as an “alarmin” released from the epithelial cells and from different human tissues and organs after a damage following, that is, an inflammatory process. The aim of this literature review is to strengthen the hypothesis about an IL-31/IL-33 axis by evaluating the most recent studies linking these two cytokines. Literature data showed that, in many cases, IL-31 and IL-33 are linked to each other and that their expression is correlated with disease severity. The presence of one interleukin might stimulate the induction of the other, amplifying inflammation and the consequent detrimental processes. In a near future, influencing their balance could be helpful in modulating the first responses of the immune system in order to prevent the development of many inflammation-related diseases.

Clonal Effect Of Lenalidomide On Akt Activation In Low-Risk MDS Patients With Del(5q)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5227-5227
Author(s):  
Matilde Y Follo ◽  
Carlo Finelli ◽  
Cristina Clissa ◽  
Sara Mongiorgi ◽  
Carmen Baldazzi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Erythroid Differentiation ◽  
Low Risk ◽  
The Other ◽  
Normal Cells ◽  
Akt Phosphorylation ◽  
Other Hand ◽  
5Q Deletion

Abstract Lenalidomide is an immunomodulating drug currently used in the treatment of del(5q) low-risk MDS patients, where it can suppress the del(5q) clone and restore a normal erythropoiesis. The exact molecular mechanisms underlying the effect of Lenalidomide in del(5q) MDS are not completely clear, although Akt phosphorylation is inhibited in Lenalidomide-sensitive del(5q) cell lines (Gandhi et al, 2006). On the other hand, the activation of the Akt/mTOR pathway has been demonstrated in CD34+ cells from high-risk MDS (Follo et al, 2007), which show alterations on stem cell proliferation, differentiation and apoptosis. These processes are important also in low-risk MDS, that usually show a stable disease but can evolve towards a worse clinical status, characterized by an increased cell proliferation. In this study we firstly investigated the effect of Lenalidomide in 6 patients with del(5q) MDS (IPSS: Low or Int-1). Given the limited number of cells, we analyzed bone marrow total mononuclear cells. As for Akt phosphorylation, we analyzed its localization along with RPS14, in order to specifically detect the del(5q) clone. On the other hand, by Real-Time PCR analyses, we assessed the expression of Globin genes, to evaluate the effect of the drug on erythropoiesis. In addition, we analyzed the effect of Lenalidomide on two cell lines with a different 5q status, one bearing a normal 5q chromosome and one showing the 5q deletion, to further investigate the effect of this drug on cell cycle, erythroid differentiation and inositide signalling pathways. Clinically, 4/6 del(5q) MDS patients showed a favourable response to Lenalidomide. At a molecular level, these cases showed an activation of erythropoiesis, in that Beta-Globin levels increased, as compared with baseline. Moreover, these subjects also displayed a specific phosphorylation of Akt. Interestingly, Akt resulted to be specifically activated in cells not showing the 5q deletion, whereas it was down-regulated in del(5q) cells. The two non responder patients early discontinued Lenalidomide for adverse events, and for these patients neither a clinical assessment of Lenalidomide effect, nor a molecular analysis, were possible. As for cell lines, ongoing analyses are showing that Lenalidomide specifically inhibits the growth of the del(5q) clone, blocking cells in G1 phase. On the other hand, Akt phosphorylation specifically increases in cells with a normal 5q chromosome. Taken together, our data show a specific activation of erythropoiesis in del(5q) low-risk MDS patients responding to Lenalidomide. In addition, our results indicate that Akt is specifically phosphorylated in normal cells without the del(5q), leading to hypothesize that Lenalidomide has a double effect: it can induce apoptosis in clonal del(5q) cells, but it also supports the proliferation and erythroid differentiation of normal cells, as also described in non-del(5q) MDS (Ebert et al, 2008). Therefore, our findings might contribute to elucidate the molecular mechanisms of Lenalidomide and possibly pave the way for the development of innovative therapeutic targeted strategies in MDS. Disclosures: No relevant conflicts of interest to declare.

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