scholarly journals Φαρμακοκινητική, φαρμακοδυναμική και φαρμακογενωμική ανάλυση της μπεβασιζουμάμπης σε ασθενείς με μεταστατικό καρκίνο του παχέος εντέρου

2019 ◽  
Author(s):  
Απόστολος Παπαχρήστος
Keyword(s):  
Wild Type ◽  
Type C

Το όφελος στη θεραπεία διαφόρων όγκων από τη μπεβασιζουμάμπη έχει διαπιστωθεί από διάφορες μελέτες. Ωστόσο, τα κλινικά αποτελέσματα εμφανίζουν μεταβλητότητα, με ορισμένους ασθενείς να ανταποκρίνονται αξιοσημείωτα καλά, ενώ κάποιοι άλλοι όχι. Οι φαρμακοκινητικές παράμετροι συγκαταλέγονται μεταξύ των σημαντικότερων παραμέτρων, οι οποίες επηρεάζουν τη δράση του φαρμάκου και την κλινική ανταπόκριση.Για την αξιολόγηση της επίδρασης διαφόρων φυσιολογικών, φαρμακοκινητικών, φαρμακοδυναμικών και γενετικών παραγόντων στα κλινικά αποτελέσματα που παρατηρούνται σε ασθενείς που λαμβάνουν πρώτης γραμμής θεραπεία με μπεβασιζουμάμπη σε συνδυασμό με χημειοθεραπεία για μεταστατικό καρκίνο του παχέος εντέρου και την προβλεπτική τους ικανότητα διεξήχθη μια προοπτική, μη παρεμβατική μελέτη παρατήρησης. Η μελέτη έγινε σε 46 ασθενείς με επιβεβαιωμένο καρκίνο παχέος εντέρου σταδίου 4 που έλαβαν πρώτης γραμμής θεραπεία με μπεβασιζουμάμπη και χημειοθεραπεία. Η διαδικασία ένταξης των ασθενών στη μελέτη διήρκησε ένα έτος. Ο χρόνος παρακολούθησης των ασθενών μετά την ένταξή τους στη μελέτη ήταν πέντε έτη. Έγινε αξιολόγηση της ανταπόκρισης στη θεραπεία, του διαστήματος ελεύθερου νόσου και της συνολικής επιβίωσης και προσδιορίστηκε η συγκέντρωση της ολικής μπεβασιζουμάμπης και του ελεύθερου VEFG165 σε ορό αίματος. Έγινε επίσης ανίχνευση των μονονουκλεοτιδικών πολυμορφισμών για τα γονίδια VEG-A και ICAM-1 σε ολικό αίμα και για τα γονίδια KRAS, NRAS και BRAF σε δείγμα καρκινικού ιστού. Η ανταπόκριση στη θεραπεία δεν επηρεάστηκε από οποιοδήποτε πολυμορφισμό στα γονίδια VEGF-A, ICAM-1, KRAS και NRAS. Αντίθετα οι μεταλλάξεις στο BRAF συνδέονταν στατιστικά σημαντικά (p=0.026) με μη ανταπόκριση στη θεραπεία. Ασθενείς ομόζυγοι για το VEGF-A rs699947 A/A παρουσίαζαν στατιστικά σημαντικά παρατεταμένο PFS και OS σε σχέση με τους ασθενείς που παρουσίαζαν την wild-type C/C μορφή του γονιδίου. Όσον αφορά το γονίδιο ICAM-1 οι ασθενείς που έφεραν το G/A αλληλόμορφο του rs1799969 παρουσίασαν στατιστικά σημαντικά μεγαλύτερη OS σε σχέση με τους φορείς του G/G. Αναφορικά με το γονίδιο BRAF βρέθηκε ότι οι ασθενείς που είχαν όγκους με τον wild-type τύπο του γονιδίου είχαν στατιστικά σημαντικά παρατεταμένη επιβίωση σε σχέση με τους ασθενείς που είχαν μεταλλαγμένο BRAF. Παρατηρήθηκε ισχυρά αρνητική συσχέτιση μεταξύ των επιπέδων ολικής μπεβασιζουμάμπης με τα επίπεδα του μοριακού της στόχου VEGF165. Ο παράγοντας που επηρέαζε κυρίως το μοντέλο πρόσδεσης ήταν το αλληλόμορφο του VEGF-Α rs699947 A/A (p=0.002). Τέλος, παρατηρήθηκε ότι όσο υψηλότερες ήταν ο συγκεντρώσεις της μπεβασιζουμάμπης τόσο αυξανόταν η OS (p=0.0003).Εάν αυτά τα ευρήματα επιβεβαιωθούν με περαιτέρω μελέτες, αυτοί οι βιοδείκτες θα μπορούσαν να ενσωματωθούν και να χρησιμοποιηθούν για την επιλογή ασθενών με mCRC, οι οποίοι θα μπορούσαν να επωφεληθούν από τις θεραπείες με μπεβασιζουμάμπη.

Myristylation is required for Tyr-527 dephosphorylation and activation of pp60c-src in mitosis

1993 ◽  
Vol 13 (3) ◽  
pp. 1464-1470
Author(s):  
S Bagrodia ◽  
S J Taylor ◽  
D Shalloway
Keyword(s):  
Kinase Activity ◽  
Tyrosine Phosphatase ◽  
Src Kinase ◽  
Indirect Evidence ◽  
Membrane Localization ◽  
Wild Type ◽  
Src Tyrosine Kinase ◽  
Amino Terminal ◽  
Membrane Bound ◽  
Type C

The chicken proto-oncoprotein c-Src is phosphorylated by p34cdc2 during mitosis concomitant with increased c-Src tyrosine kinase activity. On the basis of indirect evidence, we previously suggested that this is caused by partial dephosphorylation at Tyr-527, the phosphorylation of which suppresses c-Src kinase activity. In support of this hypothesis, we now show that treatment of cells with a protein tyrosine phosphatase inhibitor, sodium vanadate, blocks the mitotic increase in Src kinase activity. Also, we show that an amino-terminal mutation that prevents myristylation (and membrane localization) of c-Src does not interfere with the p34cdc2-mediated phosphorylations but blocks both mitotic dephosphorylation of Tyr-527 (in kinase-defective Src) and stimulation of c-Src kinase activity. Furthermore, in unsynchronized cells, the kinase activity of nonmyristylated c-Src is suppressed by 60% relative to wild-type c-Src, presumably because of increased Tyr-527 phosphorylation. Consistent with this, the Tyr-527 dephosphorylation rate measured in cell homogenates is much higher for wild-type, myristylated c-Src than for nonmyristylated c-Src. Tyr-527 phosphatase activity was primarily associated with the nonsoluble subcellular fraction. These findings suggest that the phosphatase(s) that acts on Tyr-527 is membrane bound and indicate that membrane localization of c-Src is necessary for its mitotic activation by dephosphorylation of Tyr-527.

Purification and physical properties of nematode mini-titins and their relation to twitchin

1991 ◽  
Vol 98 (4) ◽  
pp. 491-496
Author(s):  
R. Nave ◽  
D. Furst ◽  
U. Vinkemeier ◽  
K. Weber
Keyword(s):  
Caenorhabditis Elegans ◽  
Immunofluorescence Microscopy ◽  
Apparent Molecular Weight ◽  
The Body ◽  
Wild Type ◽  
Normal Muscle ◽  
Insect Muscle ◽  
C Elegans ◽  
Type C ◽  
Beta Structure

We have isolated mini-titin from the nematodes Ascaris lumbricoides and Caenorhabditis elegans under native conditions using a modification in the procedure to prepare this protein from insect muscle. The proteins have an apparent molecular weight of 600,000 and appear in oriented specimens as flexible thin rods with a length around 240–250 nm. The circular dichroism spectrum of the Ascaris protein is dominated by beta-structure. The proteins react with antibodies to insect mini-titin and also with antibodies raised against peptides contained in the sequence predicted for twitchin, the product of the Caenorhabditis elegans unc-22 gene. Antibodies to insect mini-titin decorate the body musculature as well as the pharynx of wild-type C. elegans in immunofluorescence microscopy. In the twitchin mutant E66 only the pharynx is decorated. We conclude that the mini-titins of invertebrate muscles defined earlier by ultrastructural criteria are very likely to be twitchins, i.e. molecules necessary for normal muscle contraction. We discuss the molecular properties of the proteins in the light of the sequence established for twitchin.

The Critical Role of Peptidyl-Prolyl cis/trans Isomerase, Pin1 in Acute Myeloid Leukemia with C/EBPalpha Mutations.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2213-2213
Author(s):  
J. Pulikkan ◽  
A. Peer Zada ◽  
M. Geletu ◽  
V. Dengler ◽  
Daniel G. Tenen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Dominant Negative ◽  
Pcr Analysis ◽  
Wild Type ◽  
Rt Pcr ◽  
Promoter Assay ◽  
Type C ◽  
Acute Myeloid

Abstract CCAAT enhancer binding protein alpha (C/EBPα) is a myeloid specific transcription factor that coordinates cellular differentiation and cell cycle arrest. Loss of C/EBPα expression or function in leukemic blasts contributes to a block in myeloid cell differentiation. C/EBPα is mutated in around 9% of acute myeloid leukemia (AML). The mutations reported in C/EBPα are frame shift mutations and point mutations at basic region Leucine zipper. The mutant form of C/EBPα ie C/EBPα-p30 exhibits dominant negative function over the wild type protein. The role of peptidyl-prolyl cis/trans isomerase, Pin1 in tumorogenesis and its overexpression in many cancers led us to investigate its role in acute myeloid leukemia with C/EBPα mutation. Here we show that Pin1 is upregulated in patients with acute myeloid leukemia by affymetrix analysis. By quantitative Real-Time RT-PCR analysis, we show C/EBPα-p30 could induce Pin1 transcription, while the wild type C/EBPα downregulates Pin1 expression. Luciferase promoter assay for the Pin1 promoter shows that wild type C/EBPα is able to block Pin1 promoter activity. Mean while, C/EBPα-p30 couldn’t block Pin1 promotor activity. By silencing Pin1 by RNA Interference as well as with inhibitor against Pin1 (PiB) we could show myeloid differentiation in human CD34+ cord blood cells as well as in Kasumi-6 cells as assessed by FACS analysis with granulocytic markers. We investigated the mechanism underlying the dominant negative action of C/EBPα-p30 over the wild type protein. We report that Pin1 increases the transcriptional activity of the oncogene c-jun. We also show that c-jun blocks the DNA binding and transactivation of C/EBPα protein as assessed by gel shift assay and promoter assay respectively. We have previously shown that c-jun expression is high in AML patients with C/EBPα mutation and c-jun could block C/EBPα function by protein-protein interaction. Quantitative Real-Time RT-PCR analysis shows that inhibition of Pin1 by the inhibitor PiB downregulates c-jun mRNA expression. In conclusion, inhibition of Pin1 leads to granulocytic differentiation. Our results show Pin1 as a novel target in treating AML patients with C/EBPα mutation.

Wild-Type and Mutant C-Kit Activation of Stat3α Contribute to Leukemogenesis through Distinct Effects on Myeloid Cell Proliferation and Resistance to Apoptosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5317-5317
Author(s):  
Michele Redell ◽  
Marcos J. Ruiz ◽  
David John Tweardy
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Live Cells ◽  
Proliferation Index ◽  
Detectable Effect ◽  
Wild Type ◽  
Type C ◽  
Number Of Cells ◽  
In Cells

Abstract Expression of a constitutively active mutant of the receptor tyrosine kinase c-Kit in patients with acute myeloid leukemia (AML) is associated with poor survival. Most mutations occur in the activation loop, at Asp 816 or Asn 822, resulting in ligand-independent tyrosine phosphorylation and resistance to many of the tyrosine kinase inhibitors currently in use. Signal transducer and activator of transcription 3 (Stat3) also is upregulated and/or constitutively activated in many malignancies, including AML. Stat3 is activated by both wild-type c-Kit, which is expressed on most AML blasts, and by mutant c-Kit. Like mutant c-Kit, increased Stat3 activity has been associated with poor outcome in patients with AML. Stat3 exists in two isoforms – full length Stat3α (p92) and C-terminally truncated Stat3β (p83) – and the contribution of each isoform to c-Kitmediated leukemogenesis is not known. To begin to address this issue, we generated IL-3-dependent 32D murine myeloid cells that inducibly overexpress Stat3α when treated with dexamethasone and doxycycline (induced: Stat3αHI; uninduced: Stat3αLO). We further transfected these cells with wild-type c-Kit (c-KitWT), c-KitD816H or c-KitN822K. First, we established by immunoblotting that c-Kit and Stat3α were tyrosine-phosphorylated only after stem cell factor (SCF) stimulation in cells expressing c-KitWT, but were constitutively phosphorylated in c-KitD816H and c-KitN822K cells. To test the effects of increased Stat3α on survival and proliferation, we withdrew cells from IL-3 and stimulated with SCF (100 ng/ml) for 3 days; control cells remained unstimulated. We measured the proportion of cells undergoing apoptosis at day 3 by FACS using annexin V-PE labeling. In cells expressing c-KitWT, apoptosis was significantly reduced in SCF-stimulated Stat3αHI cells compared to SCF-stimulated Stat3αLO cells (8.4 ± 5.0% v. 40.8 ± 19.9%; p<0.05). In cells expressing c-KitD816H or c-KitN822K, apoptosis was significantly reduced in Stat3αHI cells compared to Stat3αLO cells (c-KitD816H: 30.2 ± 10.2% v. 66.7 ± 8.1%, p<0.05; c-KitN822K: 25.1 ± 17.4% v. 61.4 ± 19.8%, p<0.05). SCF treatment had no detectable effect on apoptosis in cells expressing mutant c-Kit. Next, we measured the rate of proliferation using the membrane tracking dye PKH26. Fluorescence histograms, with gating on live cells, were modeled using ModFit LT, and the proliferation index (PI; total number of cells/calculated number of cells in parental generation) at day 3 was calculated. Cells expressing c-KitWT did not proliferate well in the absence of SCF-stimulation, with PIs 1.6 ± 0.1 and 2.1 ± 0.3 for Stat3αLO and Stat3αHI, respectively. The PI for SCF-stimulated Stat3αHI cells was significantly higher than the PI for SCF-stimulated Stat3αLO cells (5.4 ± 0.7 v. 3.7 ± 1.1, p<0.05). Surprisingly, cells expressing mutant c-Kit showed only low levels of proliferation, regardless of Stat3α level or SCF stimulation. The PI was 2.0 ± 0.5 in unstimulated Stat3αHI c-KitD816H cells and 2.4 ± 0.3 in Stat3αHI c-KitN822K cells. Thus, both wild-type and mutant c-Kit activate Stat3α, which results in marked resistance to apoptosis. Wild-type c-Kit also activates a distinct signaling pathway that drives proliferation, and this process is augmented by Stat3α activation. These findings suggest that the critical role for Stat3α in myeloid leukemogenesis is apoptosis prevention and that targeting Stat3α is likely to be an effective therapeutic approach for leukemias with wild-type or mutant c-Kit.

Unique Gain-of-Function of Mutated c-CBL Tumor Suppresor in Myeloid Neoplasms.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2970-2970
Author(s):  
Masashi Sanada ◽  
Takahiro Suzuki ◽  
Lee-Yung Shih ◽  
Makoto Otsu ◽  
Motohiro Kato ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Tyrosine Kinases ◽  
E3 Ubiquitin Ligase ◽  
Tumour Suppressor ◽  
Wild Type ◽  
Gain Of Function ◽  
Hematopoietic Stem ◽  
Myeloid Neoplasms ◽  
Ubiquitin Ligase Activity ◽  
Type C

Abstract Abstract 2970 Poster Board II-946 Acquired uniparental disomy (aUPD) is a common feature of myeloid neoplasms, especially myelodysplastic syndromes (MDS) / myeloploriferative neoplasms (MPN). aUPDs preferentially affected several chromosomal arms in distinct subsets of patients, and frequently associated with mutated oncogenes and tumour suppressor genes. Among these, the most common aUPDs are those involving 11q, which defined a unique subset of myeloid neoplasms that were clinically characterized by frequent diagnosis of chronic myelomonocytic leukaemia (CMML) with normal karyotypes. Recently, we and other groups reported that 11qUPD are genetically defined by the presence of homozygous mutations of C-CBL. C-CBL proto-oncogene is the cellular homolog of the v-Cbl transforming gene of the Cas NS-1 murine leukemia virus. C-CBL is thought to be involved in the negative modulation of tyrosine kinase signalling, primarily through their E3 ubiquitin ligase activity that is responsible for the down-regulation of activated tyrosine kinases. As expected from the latter function, we demonstrated that wild-type C-CBL has tumour suppressor functions; c-Cbl null mice showed expanded hematopoietic progenitor pools, promoted blastic crisis induced by a bcr/abl transgene, and spontaneous development of late-onset invasive cancers in complete penetrance. On the other hand, mutated C-CBL showed clear oncogenic potential; all tested mutants strongly transformed NIH3T3 fibroblasts, and prolonged replating capacity of hematopoietic progenitors. All reported C-CBL mutations involved the linker-RING finger domains that are central to the E3 ubiquitin ligase activity. We demonstrated that mutated C-CBL not only lost their E3 ubiquitin ligase activity, but also inhibited that of wild-type C-CBL, leading to prolonged activation of a broad spectrum of tyrosine kinases after ligand stimulations in fibroblasts and hematopoietic cells. In accordance with this, c-Cbl−/− hematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines, but unexpectedly, transduction of C-CBL mutants into c-Cbl−/− HSPCs further augmented the sensitivity to a broader spectrum of cytokines, indicating the presence of gain-of-function in mutated C-CBL that is not simply mediated by inhibition of wild-type C-CBL functions. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in the c-Cbl+/+ background or by co-transduction of wild-type C-CBL, which may suggest the pathogenic importance of loss of wild-type c-Cbl alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a novel insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some of myeloid cancer subsets. Currently, further functional studies regarding the molecular mechanism of the gain-of-function are ongoing. Disclosures: Omine: Alexion: Consultancy, Research Funding.

A Novel 2 Amino Acids Deletion in the Leucine Zipper Domain of C/EBPε Leads to Neutrophil-Specific Granule Deficiency (SGD)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4101-4101
Author(s):  
Tadayuki Akagi ◽  
Taizo Wada ◽  
Masahiro Muraoka ◽  
Tomoko Toma ◽  
Kenzo Kaji ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Wild Type ◽  
Nih3t3 Cells ◽  
Endogenous Expression ◽  
Leucine Zipper Domain ◽  
Type C ◽  
Specific Granule

Abstract Neutrophil-specific granule deficiency (SGD) is a rare congenital disorder. Neutrophils of SGD patients show abnormal bilobed nuclei and lack secondary and tertiary granule gene expression. Since neutrophils of SGD patients are deficient for bactericidal activity, the patients display immunodeficiency and suffer from frequent and severe infections. The transcription factor CCAAT/enhancer binding protein epsilon (C/EBPε) is one of the major regulators of granulopoiesis and is known to be the responsible gene for the disease. At least two homozygous germline mutations (5bp deletion and A-nucleotide insertion) of C/EBPε, which are functionally defective, have been reported. Here, we report a novel in-frame deletion of the C/EBPεgene in a 55 years-old female patient with a life-long history of recalcitrant skin infections with ulcer and scar formation. Peripheral blood smear showed characteristic changes, including reduction of cytoplasmic granules and increased bilobed nuclei of the neutrophils, monocytosis, absence of eosinophils and increased basophils. Flow cytometric examination revealed significant reduction of CD16 and abnormal expression of CD14 on the neutrophil surface. Sequencing of the C/EBPε gene revealed a homozygous deletion of 6 base-pairs (arginine and serine residues deletion; ΔRS) within the leucine zipper domain. Activation of luciferase driven by G-CSF receptor promoter was not induced by ΔRS; and endogenous expression of granule genes, including B9, NGAL and lactoferrin, was induced by wild-type C/EBPε but not by ΔRS in NIH3T3 cells, suggesting that transcriptional activity of ΔRS was diminished. GFP-tagged ΔRS, as well as wild-type C/EBPε, were localized to the nucleus in NIH3T3 cells, and DNA binding activity of ΔRS, which was determined by biotin-labeled DNA pulldown assay, was intact. Meanwhile, ΔRS together with Gata1 and PU.1 were not able to induce expression of eosinophil major basic protein (MBP) in NIH3T3 cells. Of note, wild-type C/EBPε associated with Gata1; however, ΔRS did not interact with Gata1, indicating that the ΔRS likely impairs protein-protein interaction of other transcription factors resulting in loss of transcriptional activation. These results further support the importance of the leucine zipper domain of C/EBPε for its essential function and indicate multiple molecular mechanisms leading to SGD. Disclosures No relevant conflicts of interest to declare.

Antheridiogen concentration and spore size predict gametophyte size in Ceratopteris richardii

Botany ◽  
2012 ◽  
Vol 90 (3) ◽  
pp. 175-179 ◽  
Author(s):  
Mike Ganger ◽  
Tiffany Sturey
Keyword(s):  
Sex Determination ◽  
Environmental Sex Determination ◽  
Wild Type ◽  
Ceratopteris Richardii ◽  
Spore Size ◽  
Male Development ◽  
Homosporous Fern ◽  
Type C ◽  
Slow Growing ◽  
Genetic Mutants

In many plants females invest more in reproduction than males. In organisms that exhibit environmental sex determination, individuals in low-quality environments or who are slow growing are expected to develop into males. The gametophytes of Ceratopteris richardii Brongn., a homosporous fern, may develop as males or hermaphrodites. Hermaphrodites secrete a pheromone called antheridiogen that induces undifferentiated spores to develop as males. Given that induction is not 100% in the presence of antheridiogen, it is hypothesized that resources may alter C. richardii gender decisions. An experiment was undertaken to determine (i) whether spore size predicts gender, (ii) whether spore size predicts gametophyte size, (iii) whether antheridiogen negatively affects the growth of C. richardii, and (iv) whether wild-type C. richardii and him1 mutants (genetic mutants disposed to male development regardless of antheridiogen presence) behave similarly in their response to antheridiogen. Spore size was not predictive of gender but was positively related to both male and hermaphrodite gametophyte size. Antheridiogen was found to slow the growth of male and hermaphrodite gametophytes of the wild type and male gametophytes of the him1 mutant. These results are supportive of the idea that gender may be determined indirectly through antheridiogen’s effect on gametophyte growth.

Pentacycloundecane derived hydroxy acid peptides: A new class of irreversible non-scissile ether bridged type isoster as potential HIV-1 wild type C-SA protease inhibitors

2012 ◽  
Vol 40 ◽  
pp. 19-29 ◽  
Author(s):  
Rajshekhar Karpoormath ◽  
Yasien Sayed ◽  
Patrick Govender ◽  
Thavendran Govender ◽  
Hendrik G. Kruger ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Hydroxy Acid ◽  
Wild Type ◽  
New Class ◽  
Type C ◽  
Hiv 1

scholarly journals Organization of the photosystem II centers and their associated antennae in the thylakoid membranes: a comparative ultrastructural, biochemical, and biophysical study of Chlamydomonas wild type and mutants lacking in photosystem II reaction centers.

1980 ◽  
Vol 87 (3) ◽  
pp. 728-735 ◽  
Author(s):  
F A Wollman ◽  
J Olive ◽  
P Bennoun ◽  
M Recouvreur
Keyword(s):  
Photosystem Ii ◽  
Fluorescence Analysis ◽  
Thylakoid Membranes ◽  
Reaction Centers ◽  
Type Number ◽  
Wild Type ◽  
Light Harvesting Complexes ◽  
Biophysical Study ◽  
In The Wild ◽  
Type C

We investigated the ultrastructure of thylakoid membranes that lacked either some or all of their Photosystem II centers in the F34SU3 and F34 mutants of Chlamydomonas reinhardtii. We obtained the following results: (a) There are no particles of the 160-A size class on the EF faces of the thylakoids in the absence of Photosystem II centers (as in F34); the F34SU3 contains 50% of the wild-type number of PSII centers and EF particles. (b) The density of the particles on the PF faces of the thylakoids is higher in the mutants than in the wild type. (c) The fluorescence analysis shows that the organization of the pigments is the same regardless of whether 50% of the PSII centers are temporarily inactivated (by preilluminating the wild type) or are actually missing from the thylakoid membrane (F34SU3). Our results, therefore, support a model in which: (a) each 160-A EF particle has only one PSII center surrounded by light-harvesting complexes and (b) part of the PSH antenna is associated with 80-A PF particles in both of the mutants and the wild type.

scholarly journals THE INTERGRADATION, GENETIC INTERCHANGEABILITY AND INTERPRETATION OF GENE CONVERSION SPECTRUM TYPES

Genetics ◽  
1979 ◽  
Vol 92 (1) ◽  
pp. 49-65
Author(s):  
Bernard C Lamb ◽  
Aglaia Ghikas
Keyword(s):  
Gene Conversion ◽  
Base Substitution ◽  
Meiotic Segregation ◽  
Wild Type ◽  
Conversion Frequency ◽  
Ascobolus Immersus ◽  
Asymmetric Hybrid ◽  
Type C ◽  
Conversion Spectrum ◽  
Type Strains

ABSTRACT In the Pasadena strains of Ascobolus immersus, the gene conversion propperties of 29 induced (nine UV, nine NG, and 11 ICR-170) and nine spontaneous white-ascospore mutations have been studied. Each mutant was cyossed to three types of derived wild-type strains; single mutants often gave very different conversion results in the three types of crosses, with any or all of the following changes in: percentage with post-meiotic segregation among aberrant-ratio asci; percentage with conversion to wild type among aberrant-ratio asci; and in total conversion frequency. — These results are compared with those of LEBLON (1972 a, b) from Ascobolus immersus and Yu-SUN, WICRRAMARATNE and WHITEHOUSE (1977) from Sordaria breuicollis. It is shown that conversion spectrum types are not necessarily distinct, but can completely intergrade, on the criteria of both post-meiotic segregation frequency and direction of correction. Genetic differences between strains in the present work resulted in much interchangeability of spectrum types for the same mutation in different crosses; e.g., from type C in one cross to type B/D type in another cross, although the mutation is presumably of the same molecular type (addition or deletion frame shift, or base substitution) in each cross. These changes of conversion properties for a given mutation in different crosses mean that previous interpretations of spectrum types in terms of specific conversion properties for various molecular types of mutation are inapplicable, or inadequate on their own, to explain the present data. Other factors, such as heterozygous cryptic mutations or conversion control genes, are probably involved. Because of asymmetric hybrid DNA formation, correction properties may differ from observed conversion properties.

Sign in / Sign up

Export Citation Format

Share Document