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Mutations of C-RAF Are Rare in Human Cancer because C-RAF Has a Low Basal Kinase Activity Compared with B-RAF
Victoria Emuss, Mathew Garnett, Clive Mason, The Cancer Genome Project and Richard Marais
Victoria Emuss
Mathew Garnett
Clive Mason
Richard Marais
DOI: 10.1158/0008-5472.CAN-05-1683 Published November 2005
The protein kinase B-RAF is mutated in ∼8% of human cancers. Here we show that presumptive mutants of the closely related kinase, C-RAF, were detected in only 4 of 545 (0.7%) cancer cell lines. The activity of two of the mutated proteins is not significantly different from that of wild-type C-RAF and these variants may represent rare human polymorphisms. The basal and B-RAF–stimulated kinase activities of a third variant are unaltered but its activation by RAS is significantly reduced, suggesting that it may act in a dominant-negative manner to modulate pathway signaling. The fourth variant has elevated basal kinase activity and is hypersensitive to activation by RAS but does not transform mammalian cells. Furthermore, when we introduce the equivalent of the most common cancer mutation in B-RAF (V600E) into C-RAF, it only has a weak effect on kinase activity and does not convert C-RAF into an oncogene. This lack of activation occurs because C-RAF lacks a constitutive charge within a motif in the kinase domain called the N-region. This fundamental difference in RAF isoform regulation explains why B-RAF is frequently mutated in cancer whereas C-RAF mutations are rare.
C-RAF
B-RAF
The protein kinases of the RAF family, mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) family, and ERK family form a three-tiered cascade that is activated in a RAS-dependent manner and which is an important regulator of cell fate decisions ( 1, 2). There are three RAF proteins in mammals, A-RAF, B-RAF, and C-RAF, and they share three conserved regions: CR1 and CR2 within the regulatory NH2 terminus and CR3 encompassing the kinase domain within the COOH terminus (see Fig. 1 ). RAF proteins are normally cytosolic but they are recruited to the plasma membrane by the small G-protein RAS, and this is an essential step for their activation by growth factors, cytokines, and hormones. At the membrane, RAF activation occurs through a highly complex process involving conformation changes, binding to other proteins, binding to lipids, and phosphorylation and dephosphorylation of some residues ( 3, 4).
Amino acid changes in C-RAF. A, schematic of C-RAF. Light shaded boxes, CR1, CR2, and CR3; dark shaded boxes, N-region and the activation segment (Act. Seg.). The positions of the four mutations identified in C-RAF in the cancer cell lines are also indicated. B, alignment of the amino acid sequences for specific regions of A-RAF, B-RAF, and C-RAF from humans (Hs), mice (Mm), chickens (Gg), Xenopus (Xe), zebra fish (Dr), Drosophila melanogaster (Dm), and C. elegans (Ce). Mutations present in C-RAF in human cancer; bold, conserved in the other species. Gray box, N-region.
Within the kinase domain, phosphorylation of two motifs is required for activation. One of these is called the activation segment, which must be phosphorylated on conserved threonine and serine residues. In B-RAF, these are T599 and S602 (originally designated as T598 and S601 due to a sequencing error in the database; ref. 5) and in C-RAF, the corresponding residues are T491 and S494. Structural studies have revealed that when the activation segment is not phosphorylated, it binds to another region of the kinase domain called the glycine-rich loop, trapping B-RAF in an inactive conformation. T599 phosphorylation is thought to disrupt this interaction, releasing the activation segment and reorientating critical residues into the correct position for catalysis ( 6). Presumably, similar mechanisms operate in the other isoforms.
The other motif that must be phosphorylated is called the negative-charge regulatory or N-region. The N-region controls a fundamental difference in how the RAF proteins are regulated. In C-RAF, the N-region sequence is 338SSY341Y and phosphorylation of S338 and Y341 is essential for activation by RAS and growth factors. Both sites are conserved in A-RAF (S299 and T302, respectively) but in B-RAF, Y340 and Y341 are replaced by aspartic acids (D448 and D449) and although S338 is conserved, it is constitutively phosphorylated ( 7). All RAF isoforms are only fully activated when four negative charges occupy the N-region, either from the phosphorylated serine and tyrosine or from the phosphorylated serine and aspartic acids. However, whereas the charges are present constitutively in B-RAF, in A-RAF and C-RAF they are only acquired under activating conditions. Consequently, the basal kinase activity of B-RAF is considerably higher than that of A-RAF and C-RAF and whereas the latter two need both RAS and SRC for activation, B-RAF is fully activated by RAS alone ( 8). Importantly, for all isoforms, activation segment phosphorylation and, in the case of A-RAF and C-RAF, N-region phosphorylation occur at the plasma membrane, in part explaining why membrane recruitment is essential for RAF activation by RAS and membrane-bound receptors.
We recently described a systematic sequencing approach that allowed us to identify somatic gain-of-function mutations in the B-RAF gene in ∼8% of human cancers ( 5, 9). Importantly, a glutamic acid substitution for the valine at codon 600 (V600) accounts for ∼90% of the B-RAF mutations, demonstrating extraordinary selection for this genetic lesion. V600EB-RAF is activated ∼500-fold; it stimulates constitutive MEK-ERK signaling in cells and transforms fibroblasts and melanocytes ( 6, 9– 12). Over 45 other cancer-associated mutations have been described in B-RAF, the majority clustering to the glycine-rich loop and the activation segment, the two regions of the kinase domain that are responsible for trapping B-RAF in the inactive conformation ( 5). These mutations are thought to activate B-RAF by disrupting the inactive conformation of the kinase and allowing the active conformation to prevail ( 6).
It is clear that B-RAF is important in human cancer but the role(s) of A-RAF and C-RAF is less evident. In this study, we screen 545 cancer cell lines and over 100 tumor samples for mutations in A-RAF and C-RAF. We describe four coding region changes that were identified in C-RAF but do not find any such mutations in A-RAF. However, these presumed mutations in C-RAF have weak effects on C-RAF kinase activity and none of them converts C-RAF into a transforming oncogene. We have also created a V492E substitution in C-RAF to mimic the common V600E mutation of B-RAF and find that this also has only weak kinase activity and lacks NIH 3T3 transforming activity. The lack of C-RAF activation by these mutations seems to be due to the lack of intrinsic charge within the N-region, demonstrating that this motif reveals the oncogenic potential of B-RAF and explaining why C-RAF is not frequently mutated in human cancer.
Genomic sequencing was done as described ( 9) using the primers shown in Supplementary Table 1. Expression constructs for G12VRAS, C-RAF, and B-RAF have been described ( 8). Additional B-RAF and C-RAF substitutions were generated by PCR mutagenesis and verified using automated dideoxy sequencing. COS7 cells and NIH 3T3 cells were maintained in DMEM (Life Technologies, Paisley, Scotland) supplemented with 10% or 5% FCS, respectively. COS7 cells were transfected with LipofectAMINE (Invitrogen, Carlsbad, CA) as described ( 8). NIH 3T3 transformation assays were done as described ( 6). Preparation of COS cell lysates, Western blotting, protein expression measurements, and RAF-coupled kinase assay have all been described previously ( 7, 8, 13). Blotting for pS338 phosphorylated C-RAF was done as described ( 7). Blotting for phosphorylated MEK was done using standard techniques and a ppMEK1/2 antibody (9121L, Cell Signaling Technology, Beverly, MA).
C-RAF mutations are rare in human cancer. We previously identified 43 mutations in the B-RAF gene when we sequenced the exons and intron-exon boundaries in 545 cancer cell lines but did not observe any mutations in 341 normal DNA samples ( 9). Here we have also sequenced all 16 exons of the C-RAF gene and all 15 exons of the A-RAF gene in these cancer cell lines and normal DNA samples, comparing the data to the sequences of A-RAF and C-RAF available on the National Center for Biotechnology Information database. 3 Whereas 7.9% of the cancer cell lines have mutations in B-RAF, only four (0.73%) have coding region variations that result in amino acid changes in C-RAF, and there were no such mutations in A-RAF. We did not observe any such changes in either A-RAF or C-RAF in the normal DNA samples. The presumptive C-RAF mutations are a serine for proline substitution at position 207 (P207S) in SW684 fibrosarcoma cells; an isoleucine for valine at 226 (V226I) in ChaGo-K-1 lung carcinoma cells; a histidine for glutamine at 335 (Q335H) in NCI-H2087 lung adenocarcinoma cells; and a lysine for glutamic acid at 478 (E478K) in Ls513 colorectal carcinoma cells ( Table 1 ).
C-RAF mutations in human cancer cell lines
We have also sequenced A-RAF and C-RAF from primary tumors from 18 breast cancers, 26 lung cancers, 15 testis cancers, and 20 gastric cancers. In addition, we have sequenced C-RAF from 30 colorectal cancers and its kinase domain from an additional 10 gliomas, 9 acute lymphoid leukemias, and 20 myeloproliferative disease samples. Finally, we have sequenced the A-RAF kinase domain from 10 gliomas. We have not detected either A-RAF or C-RAF mutations in any of these primary tumors, again demonstrating that C-RAF mutations are rare and A-RAF mutations are rare or nonexistent.
The P207S, V226I, and E478K substitutions do not occur coincident with mutations in either B-RAF or any of the RAS genes whereas Q335H occurs coincident with activating mutations in both B-RAF (L597V) and N-RAS (Q61K) in NCI-H2087 cells ( Table 1). P207 and V226 are between CR1 and CR2 in a region of the protein of which function is unknown; Q335 is between CR2 and CR3, three residues upstream of the N-region; and E478K is within the kinase domain ( Fig. 1). P207, V226, and Q335 are reasonably well, but not absolutely, conserved in C-RAF from several species but they are not conserved in A-RAF or B-RAF from any species or, with the exception of Q335 in Caenorhabditis elegans, in the single RAF paralogues from lower organisms ( Fig. 1B). In contrast, E478 is highly conserved, with glutamic acid being found at the corresponding position in all RAF orthologues and paralogues from lower and higher organisms. Indeed, a review of the human genome reveals that 27.6% of all human kinases possess a glutamic or aspartic acid at the corresponding position (data not shown), demonstrating a strong selection for an acidic amino acid at this position in many kinases. Importantly, there are no reports showing that the amino acids in B-RAF that correspond to P207, V225, and Q335 (T312, T330, and R443, respectively) are mutated in human cancer whereas the equivalent of E478 (E586 in B-RAF) is mutated and, intriguingly, also to a lysine ( 9). E586KB-RAF has ∼130-fold elevated kinase activity ( 6).
P207S, V226I, and Q335H substitutions do not activate C-RAF. For characterization, we expressed myc-epitope tagged versions of these presumptive C-RAF mutants in COS cells and measured their activity in a kinase cascade assay using glutathione S-transferase (GST)-MEK, GST-ERK, and myelin basic protein as substrates, with ATP at a physiologically relevant concentration of 5 mmol/L ( 6). Under these conditions, C-RAF has low basal kinase activity but is activated 80- to 120-fold by oncogenic RAS (G12VRAS; Fig. 2A and B ). The basal kinase activities of P207SC-RAF and V266IC-RAF are similar to that of WTC-RAF and their activation by G12VRAS is also similar to that of WTC-RAF although it was consistently lower ( Fig. 2A and B). In line with their lack of elevated basal kinase activity, these mutants do not activate MEK in COS cells ( Fig. 2C) and they do not transform NIH 3T3 cells ( Fig. 2D).
Characterization of P207SC-RAF, V226IC-RAF, and Q335HC-RAF. A, basal kinase activity; B, G12VRAS-activated kinase activity. Columns, mean from one assay done in triplicate; bars, SD. Similar results were obtained in at least three experiments. C, Western blot for C-RAF, ppMEK, and total MEK in COS cells expressing C-RAF or the indicated mutants. Oncogenic RAS was included where indicated. D, NIH 3T3 transformation assay. Transformation efficiency of NIH 3T3 cells by C-RAF (WT) or the indicated mutants. V600EB-RAF is included as a positive control. Columns, mean of three independent determinations; bars, SD. Right, representative results from one assay.
The basal kinase activity of Q335HC-RAF is also not elevated compared with that of WTC-RAF ( Fig. 2A) and this variant also fails to activate MEK in COS cells ( Fig. 2C) or to transform NIH 3T3 cells ( Fig. 2D). However, Q335HC-RAF activation by G12VRAS was impaired and only reached 20% to 25% of the levels seen with WTC-RAF ( Fig. 2B). Because Q335 is only three amino acids upstream of the N-region of C-RAF ( Fig. 1A), we examined if the reduced activation of Q335HC-RAF is due to disrupted S338 phosphorylation. Using an antibody that only binds to C-RAF when S338 is phosphorylated ( 7), we find that antibody binding is significantly reduced in Q335HC-RAF ( Fig. 3A ). One interpretation of this result is that the Q335H substitution disrupts antibody binding and not S338 phosphorylation; thus, we used an alanine-scan mutagenic approach to define that epitope. Antibody binding is disrupted when R336, D337, and S338 are mutated to alanine, but importantly not when Q335 is mutated ( Fig. 3B). Thus, the antibody epitope seems to be "RDpS" and we conclude that Q335 is not part of it and that S338 phosphorylation on Q335HC-RAF is reduced in the presence of G12VRAS. Finally, because Q335HC-RAF occurs coincident with L597VB-RAF in NCI-H2087 cells ( Table 1) and we recently reported the surprising finding that mutant forms of B-RAF can activate WTC-RAF ( 6), we tested whether Q335HC-RAF can be activated by L597VB-RAF. Unlike the differences observed with G12VRAS, L597VB-RAF activates Q335HC-RAF and WTC-RAF to similar levels ( Fig. 3C).
RAS-dependent phosphorylation of Q335HC-RAF is impaired but its activation by mutant B-RAF is unaltered. A, Western blot for C-RAF and pS338 in COS cells expressing WTC-RAF or Q335HC-RAF. Where indicated, oncogenic RAS was coexpressed. B, Western blot for pS338 and total C-RAF in COS cells expressing C-RAF or the indicated mutants. Where indicated, oncogenic RAS was coexpressed. C, G12VRAS- and L597VB-RAF–stimulated C-RAF kinase activities. Columns, mean from one assay done in triplicate; bars, SD. Similar results were obtained in at least two experiments.
The E478K substitution activates C-RAF. In contrast to the other presumptive mutants, the E478K variant does have elevated kinase activity, its basal kinase activity being 25-fold higher than that of WTC-RAF ( Fig. 4A ). The activation of C-RAF by E478K compares poorly to the enhanced activity of E586KB-RAF, which we have shown is ∼130-fold more active than WTB-RAF ( 6). Importantly, whereas E586KB-RAF stimulates strong constitutive MEK-ERK signaling in COS cells ( 6, 14), MEK activation by E478KC-RAF is weak ( Fig. 4B); furthermore, whereas E586KB-RAF transforms NIH 3T3 cells, E478KC-RAF does not ( Fig. 4C). Remarkably, however, whereas WTC-RAF is activated ∼100-fold by G12VRAS, E478KC-RAF is activated over 500-fold ( Fig. 4A), producing a level of activation that is an impressive 13,000- to 14,000-fold higher than the basal activity of WTC-RAF. Thus, E478KC-RAF is hypersensitive to activation by oncogenic RAS, suggesting that this mutant can be strongly activated by secondary signals.
E478KC-RAF has elevated kinase activity but is not an oncogene. A, basal and G12VRAS-stimulated C-RAF kinase activities. Columns, mean from one assay done in triplicate; bars, SD. Activities are expressed as fold activation with respect to the wild-type protein. B, Western blot for C-RAF, ppMEK, and total MEK in COS cells expressing C-RAF or the indicated mutants. C, NIH 3T3 transformation assay. Transformation efficiency of NIH 3T3 cells by C-RAF or B-RAF (WT) or the indicated mutants. Columns, mean of three independent assays; bars, SD. Right, representative results from one assay. D, C-RAF kinase activity; E, B-RAF kinase activity. Columns, mean from a single assay done in triplicate; bars, SD. Similar results were obtained in at least three independent experiments.
We were intrigued by the distinct responses of C-RAF and B-RAF to the E478K/E586K mutations and wished to investigate the molecular mechanism underlying this difference. As described in Introduction, a key difference in regulation of the RAF proteins is mediated by their N-regions; thus, we tested whether this region determines how C-RAF and B-RAF respond to the E478K/E586K mutations. Y340 and Y341 of C-RAF were substituted with aspartic acids (creating DDC-RAF) to mimic the N-region of B-RAF ( Fig. 1B). As previously shown ( 14, 15), this double-substituted protein is weakly activated (∼3-fold; not obvious in Fig. 4D) but, strikingly, it synergizes with E478K (DD,E478KC-RAF) to activate C-RAF over 10,000-fold, a level that is commensurate with the activity of E586KB-RAF ( Fig. 4D). DDC-RAF also synergizes with E478KC-RAF to activate MEK in COS cells ( Fig. 4B) and to transform NIH 3T3 cells ( Fig. 4C).
We also did the reverse experiment, neutralizing the charge within the N-region of E586KB-RAF by substituting S446, S447, D448, and D449 with alanines (AAAA,E586KB-RAF). Introducing these substitutions into E586KB-RAF significantly reduces its kinase activity ( Fig. 4E) and to dissect the contributions made by the individual charged amino acids within the N-region, we independently substituted S446/S447 and D448/D449 with alanines. Both the S446A/S447A (AADD,E586KB-RAF) and the D448A/D449A (SSAA,E586KB-RAF) substituted proteins have significantly reduced kinase activity ( Fig. 4E), demonstrating that S446 phosphorylation and the aspartic acids of the N-region both contribute to the elevated kinase activity of E586KB-RAF. Finally, we show that the transforming activity of E586KB-RAF is significantly reduced when the N-region charge is disrupted ( Fig. 4C). We conclude that E478KC-RAF is strongly activated by mutations that introduce a constitutive negative charge into its N-region whereas the activity of E586KB-RAF is compromised by the inverse changes.
C-RAF activation by the V492E substitution is weak because its N-region lacks charge. We were intrigued to note that whereas V600 of B-RAF is mutated in 6% to 7% of human cancers ( 5), we did not observe any mutations of the equivalent codon (V492) in C-RAF in our 545 cancer cell lines or the 148 primary tumor samples. We therefore tested how a V492E substitution affected C-RAF kinase activity. V492EC-RAF is ∼45-fold more active than WTC-RAF ( Fig. 5A ), a level of activation that contrasts strongly with the ∼500-fold activation seen with the corresponding mutation in B-RAF (V600EB-RAF; ref. 6). Furthermore, whereas V600EB-RAF stimulates strong constitutive MEK/ERK signaling in mammalian cells ( 9) and is transforming ( Fig. 2D), V492EC-RAF only stimulates weak MEK activity in COS cells ( Fig. 5B) and does not transform NIH 3T3 cells ( Fig. 5C).
C-RAF is not activated by the V492E mutation and is not transforming. A, C-RAF kinase activity. Columns, mean from one assay done in triplicate; bars, SD. Activities are expressed as fold activation with respect to the wild-type protein and similar results were obtained in at least three experiments. B, Western blot for C-RAF, ppMEK, and total MEK in COS cells expressing C-RAF or V492EC-RAF. Where indicated, G12VRAS was coexpressed. C, NIH 3T3 transformation assay. Transformation efficiency of NIH 3T3 cells by C-RAF or B-RAF (WT) or the indicated mutants. Columns, mean of three independent assays; bars, SD. Right, representative results from one assay.
Once again, we were struck by the different responses of C-RAF and B-RAF to this conserved mutation; thus, we examined if this is also due to the lack of N-region charge in C-RAF. When the V492EC-RAF mutation is combined with DDC-RAF (DD,V492EC-RAF), there is a synergistic augmentation in kinase activity, resulting in a kinase of which basal activity is elevated over 1,000-fold ( Fig. 6A ). There is also a synergistic activation of MEK in COS cells ( Fig. 6B) and a synergistic augmentation of transforming activity ( Fig. 6C).
V492EC-RAF becomes activated and transforming when negative charge is introduced at the N-region. A, basal and, where indicated, RAS-stimulated kinase activities. Columns, mean from one assay done in triplicate; bars, SD. Activities are expressed as fold activation with respect to the wild-type protein and similar results were obtained in at least three experiments. B, Western blot for C-RAF, ppMEK, and total MEK in COS cells expressing C-RAF or the specified mutants. Where indicated, G12VRAS was coexpressed. C, NIH 3T3 transformation assay. Transformation efficiency of NIH 3T3 cells by WTC-RAF or WTB-RAF or the indicated mutants. Columns, mean of three independent assays; bars, SD. Right, representative results from one assay.
Finally, we did the reverse experiment, neutralizing the N-region of V600EB-RAF by creating AAAA,V600EB-RAF. This causes an ∼15-fold reduction in kinase activity but we note that the kinase is still ∼35-fold more active than WTB-RAF ( Fig. 7A ). Importantly, AAAA,V600EB-RAF still activates MEK in COS cells ( Fig. 6B) and transforms NIH 3T3 cells ( Fig. 7C) albeit at reduced levels.
The kinase activity of V600EB-RAF is impaired by neutralization of N-region charge but it is still transforming. A, B-RAF kinase activity. Columns, mean from one assay done in triplicate; bars, SD. Activities are expressed as fold activation with respect to WTB-RAF and similar results were obtained in at least three experiments. B, Western blot for B-RAF, ppMEK, and total MEK in COS cells expressing wild-type B-RAF or the specified mutants. C, NIH 3T3 transformation assay. Transformation efficiency of NIH 3T3 cells by WTB-RAF or the indicated mutants. Columns, mean of three independent assays; bars, SD. Right, representative results from one assay.
We have identified four coding region variants in C-RAF that occur in human cancer cell lines but are not seen in normal DNA samples. These four variants convert P207 to serine, V226 to isoleucine, Q335 to histidine, and E478 to lysine. Dealing with P207S and V226I first, we did not detect any significant changes in either their basal or RAS-stimulated kinase activity when MEK was used as a substrate. It is possible that these substitutions affect other currently unknown and MEK-independent functions of C-RAF; however, P207 and V226 are located in a region of the protein of which function is unknown and they are not even conserved in all C-RAF orthologues or in other RAF paralogues from a variety of higher and lower organisms. Furthermore, the corresponding residues are not mutated in B-RAF in human cancer. One interpretation of our data is that these variants are rare single-nucleotide polymorphisms that play no role in the growth of the cancer cell lines in which they were identified. If they are single-nucleotide polymorphisms, they have not been previously described 4 and we did not observe them in our 341 normal DNA samples, suggesting that they are extremely rare. An alternative explanation is that these are somatic mutations that occur due to collateral DNA damage during the development of these cancers or that have occurred in the cell lines during in vitro culture. Unfortunately, in the absence of control DNA from the patients from whom the cell lines were derived, it is not possible to determine which of these possibilities is correct. Whatever their genesis, it seems that these variants do not have an obvious effect on signaling or a clear effect on proliferation and with the caveat that their effects may only be evident in specific cell types, it seems unlikely that they play a significant role in human cancer.
Q335 is also not conserved in all C-RAF orthologues or in the other RAF paralogues. However, it is three amino acids upstream of the N-region and although this substitution also fails to affect C-RAF basal kinase activity, it does suppress its activation by oncogenic RAS. Our alanine-scan mutagenesis data show that Q335 is not part of the pS338 antibody epitope, which is consistent with the fact that this antibody binds to B-RAF when S446 is phosphorylated ( 7) and B-RAF has an arginine at the position equivalent to Q335 ( Fig. 1B). Our data suggest that the Q335H substitution disrupts S338 phosphorylation in the presence of G12VRAS, causing reduced C-RAF activation. It is not surprising that such a subtle substitution should have such a profound effect. With the exception of Q335, the amino acids surrounding the N-region of C-RAF and B-RAF are well conserved ( Fig. 1B), and yet, whereas S338 is only phosphorylated at the plasma membrane, S446 is phosphorylated in the cytosol, demonstrating exquisite selectivity by the kinases involved. Finally, our data show that the Q335H substitution does not affect C-RAF activation by L597VB-RAF, which is consistent with our recent finding that B-RAF activates C-RAF through a distinct mechanism that is largely independent of S338 phosphorylation. 5
We have been unable to study the biological function of Q335HC-RAF because we have not been able to apply RNA interference technology to NCI-H2087 cells. However, it has been shown that excessive ERK signaling can induce cell cycle arrest or senescence through induction of cell cycle inhibitory proteins such as p27 and p21 ( 16– 21). Thus, in cancer, ERK signaling must be kept within narrow limits that are sufficient to stimulate proliferation but not so high as to induce cell cycle arrest. We speculate that in some cancers, mutations or other upstream events that stimulate excessive pathway activity are incompatible with proliferation. This may be a protective mechanism but in these circumstances, precancerous cells must develop strategies to tone down this signaling to progress. We and others recently reported the identification of mutant forms of B-RAF involving residue D594 in human cancer that are devoid of kinase activity ( 6, 12, 22). These account for ∼1% of B-RAF mutations, and thus are too common to be random, and similar mutations are not observed in either C-RAF or A-RAF. Importantly, although coincident mutations in B-RAF and RAS are very rare in human cancer ( 9), ∼30% of the inactive mutants occur in cancers that also harbor RAS mutations and we have argued that the D594 mutants could act in a dominant-negative manner to suppress excessive RAS-MEK signaling ( 5). Thus, it is intriguing that in addition to the Q335HC-RAF substitution, NCI-H2087 cells harbor activating mutations in B-RAF and N-RAS, which is, to our knowledge, the only example of a cancer cell line harboring amino acid changes in three components of this pathway. Perhaps if oncogenic RAS and activated B-RAF both activate C-RAF, MEK signaling is excessive and the Q335H mutation is required to reduce signaling from one of these upstream inputs. Thus, this mutant could be acting in a dominant-negative manner and we are currently developing genetic approaches to test this model.
It is clear that B-RAF is important in human cancer and in the classic sense, it is an oncogene because activated forms can transform immortalized fibroblasts and other cell lines. Critically, "oncogenic" B-RAF does not induce cancer by itself because a high proportion of common nevi harbor mutations in the B-RAF gene but are not cancerous ( 23). Notably, of the variants we identified, only E478KC-RAF has elevated kinase activity, and yet even this mutant does not seem to be a classic oncogene because it does not transform NIH 3T3 cells. However, it is hypersensitive to activation by RAS and synergizes with the Y340D/Y341D double mutations to activate C-RAF and augment transforming activity. Thus, perhaps the oncogenic potential of E478KC-RAF is only apparent in some cell contexts. In common with P207SC-RAF and V226IC-RAF, we cannot determine whether Q335HC-RAF and E478KC-RAF are somatic mutations or rare human polymorphisms. However, because Q335HC-RAF and E478KC-RAF lack significantly elevated basal kinase activity and are not transforming, it is possible that they could be rare polymorphisms that predispose their carriers to specific forms of cancer; further studies are under way to examine this possibility.
It may be surprising that A-RAF and C-RAF mutations in cancer are so rare because both isoforms can be converted into transforming agents in experimental systems, typically by removing their NH2-terminal regulatory domains (for review, see ref. 24). Indeed, a chromosomal inversion that essentially creates just this type of agent in B-RAF has been identified in a single case of human thyroid cancer linked to the Chernobyl nuclear accident ( 25). However, the genetic approach that we use cannot identify large deletions, gene inversions, or translocations, and thus it is possible that they were present in our samples but went undetected. Another surprise is that previous experimental approaches have been used to induce transforming point mutations in full-length C-RAF, most of which are outside the kinase domain and a surprisingly large number are within CR2 ( 26– 28), and yet we did not detect any corresponding mutations in our samples. Thus, although it is possible to create oncogenic versions of C-RAF, in practice mutations in human cancer seem to be almost exclusively in B-RAF. This suggests that either the rates of mutation of the RAF genes differ significantly or the regulatory networks of the different isoforms differ in such a manner as to select against A-RAF and C-RAF mutations.
Notwithstanding this reasoning, our data provide another rational explanation of why C-RAF mutations are rare in human cancer. We show that the V492E substitution activates C-RAF ∼45-fold and over 1,000-fold when the N-region is charged. Similarly, V600E activates B-RAF ∼500-fold, unless the N-region is neutralized, then this decreases to ∼35-fold. Clearly, the V492/V600 mutations cooperate with N-region charge to activate the RAF proteins and, working in conjunction, they act to convert C-RAF into an oncogene. Similar results are seen with the E478K mutation, demonstrating the importance of the N-region in revealing the transforming potential of the mutant C-RAF proteins. Presumably in the absence of this N-region charge, even if C-RAF mutations did occur in cancer, they would not enhance its activity sufficiently to convert C-RAF into an oncogene and, hence, they do not provide an advantage and so are not selected. Alternatively, if they occurred coincident with a second event, they may even stimulate excessive signaling and actually antagonize tumor progression. Presumably, the same holds true for A-RAF.
Although the N-region clearly plays an important role in augmenting the response of the RAF proteins to the mutants, this is not the only region that seems to reveal the oncogenic potential of B-RAF. We note that when the N-regions of E586KB-RAF and V600EB-RAF are neutralized, they retain some transforming activity. We have previously shown that the basal kinase activity of B-RAF is considerably higher than that of C-RAF ( 8) and it is clear that E586KB-RAF and V600EB-RAF have even higher basal kinase activities. We show here that C-RAF must be activated over 10,000-fold to achieve the same level of activity as E586KB-RAF, and yet this is still only ∼25% of the activity of V600EB-RAF. Furthermore, although DD,V492EC-RAF is over 1,000-fold more active than WTC-RAF, this is still only 2% to 5% of the activity of V600EB-RAF. Presumably, this explains why AAAA,V600EB-RAF is still transforming: its activity is about 2,500-fold above that of WTC-RAF. Thus, although the N-region is clearly important, it is not the only factor contributing to the elevated basal kinase activity of B-RAF. Further analysis of the differences between these proteins is warranted and it does not seem to be simply due to the fact that C-RAF cannot be activated to the same level as B-RAF, as shown with DD,E478KC-RAF.
We conclude that it is the key differences between B-RAF and C-RAF that regulate the different levels of basal kinase activities that account for the fact that whereas B-RAF mutations occur in ∼8% of cancers, C-RAF mutations are rare and only occur in specific cellular contexts. Finally, we note that our data could be interpreted to suggest that approaches to target the kinase responsible for phosphorylating the N-region of B-RAF would not provide effective anticancer therapies because residual transforming is activity retained. However, if agents such as these were combined with agents that directly target oncogenic B-RAF kinase activity, they could be of considerable value.
Grant support: Cancer Research UK grant C107/A3096, The Institute of Cancer Research, and The Wellcome Trust.
Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
M. Garnett is currently at the Department of Oncology, Hutchison/Medical Research Council Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, United Kingdom. C. Mason is currently at the Molecular Sciences Sareum Ltd., 2 Pampisford Park, London Road, Pampisford, Cambridge CB2 4EE, United Kingdom.
↵3 http://www.ncbi.nlm.nih.gov/entrez/.
↵4 http://www.ncbi.nlm.nih.gov/.
↵5 M. Garnett and R. Marais, submitted for publication.
Received May 16, 2005.
Revision received July 11, 2005.
Accepted August 31, 2005.
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HomeGeneral News10/22 Links Pt1: Jordan terminating peace treaty annexes start of a process, not the end; Amb. David Friedman will now serve all of Jerusalem; Antisemitism: Judas Slur on Jewish Voters
10/22 Links Pt1: Jordan terminating peace treaty annexes start of a process, not the end; Amb. David Friedman will now serve all of Jerusalem; Antisemitism: Judas Slur on Jewish Voters
October 22, 2018 Ian General News
http://elderofziyon.blogspot.com/2018/10/1022-links-pt1-jordan-terminating-peace.html
From Ian:
Jordan terminating peace treaty annexes start of a process, not the end
Jordan's announcement on Sunday that it wanted to opt out of annexes from its 1994 peace treaty with Israel that leased two border areas that historically were difficult to delineate to Israel is a sign that not all is well in ties between the two countries. .
More precisely, not all is well in ties between Israel and the Jordanian people.
The government to government ties between Jerusalem and Amman are strong, with both sides recognizing that while the other might not always do what they want, both their interests are supremely served by peace and cooperation. Where there is a problem is at the people to people level, or, more precisely, at the Jordanian people.
In very general terms, it's fair to say that the 1994 peace agreement did not filter down to Jordanian masses. The Jordanians might already be drinking Israeli water, are scheduled to be heating their homes with Israeli natural gas in 2020, and benefit in numerous ways from security cooperation with Israel, but, for the most part, they don't like Israel.
And this is something that King Abdullah II has to take into account.
Jordan's announcement on Sunday regarding the Naharayim (Baqura) area near the Kinneret and part of Zofar (al Ghamar), in the Arava, did not knock anyone off their chair in Jerusalem. There has been talk for months inside Jordan of the need to regain those two areas. There have been debates in parliament, and even protests on the streets – much of it led by Islamic elements inside the Hashemite Kingdom.
Abdullah is in vice. While he needs the peace treaty with Israel for the security of his regime, he has domestic Islamic elements to deal with and at times placate. He is also dealing with Syrian crisis, which has not only inundated his country with refugees, but also put Iran perilously close.
The language Abdullah used in announcing the move – Jordanian land, Jordanian interests– is a bone thrown to the Islamists.
A move that spells weakness
The late Prime Minister Yitzhak Rabin saw the 1994 peace treaty with Jordan as one of his most important diplomatic achievements, if not the most important one. Unlike the skepticism he expressed over the Oslo Accords and then-PLO Chairman Yasser Arafat's commitment to them, Rabin was sure that King Hussein would live up to his word.
There is something symbolic in the fact that on the anniversary of Rabin's assassination according to the Hebrew calendar, King Abdullah announced that he would not renew one of the annexes his father signed 24 years ago, leasing agricultural borderlands to Israel.
The Jordanian announcement is neither a big surprise nor a move that has far-reaching strategic significance. After all, these are Jordanian lands and it stands to reason that Jordan would have reimposed its sovereignty over them at some point, as no country in the Middle East would ever agree to relinquish territories over time.
Saudi Arabia did the same with respect to Tiran and Sanafir islands, which were administered by Egypt for years before Riyadh reimposed its sovereignty over them in 2017.
The problem, therefore, is not in the move per se, but in the manner and timing in which the Jordanians chose to declare they were essentially disavowing the spirit of the 1994 peace agreement and turning their backs on the partnership forged between Rabin and Hussein.
Jordan nixing of land leases could sow distrust, but some see hope for reversal
Several analysts said that while the king's decision was likely the result of heavy lobbying by opponents of the peace agreement with Israel, it was still possible for Israel to maintain its access to Naharayim and Tzofar.
"I think that the negotiations between the two sides may result in a different situation whereby the two governments may agree to continue, to extend the validity of this annex concerning to these two pieces of land between them," said Oded Eran, a senior research fellow at the Institute for National Security Studies and former Israeli ambassador to Jordan.
"We have leverage. There are so many interests that we have with Jordan," said Robbie Sabel, a former legal adviser to Israel's Foreign Ministry who was involved in the Israeli-Jordanian peace negotiations.
Water and security are just two of the main areas where Jerusalem and Amman cooperate very closely, he noted.
"What we want to do is solve this issue quietly. We're not going to threaten Jordan; that would not be in our interest. It is in Israel's interest to have a secure and stable Jordan. Jordan is a strategic ally, though it's not an ally based on friendship."
Alan Baker, another former Foreign Ministry legal adviser who played an important role in drafting the 1994 peace treaty, said there was fifty-fifty chance that Israel could get Jordan to rethink its decision to terminate the annex about Naharayim and Tzofar.
While the Hashemite kingdom was perfectly in its right to reclaim these areas, Israel has "sovereign prerogatives of our own that Jordanians enjoy," such as the right to fly over Israeli airspace.
"This is not a one-way street," he said. "There are two sides. The Jordanian government, public and security establishment all enjoy various aspects of the peaceful relationship, and they want to continue to enjoy it and even enhance it. Hence, there's plenty of room to discuss the nature of the bilateral relationship."
Under Oslo Agreements, PA obliged to ensure "free access" and worship – even bus stops – for 12 specified Jewish Holy Sites. Today, all remain completely unaccessible. Instead of free access & worship, they are just free of worship. Hello @UNESCO @UNHumanRights @hrw @AmnestyCIJ? pic.twitter.com/s08kBlR9WW
— Eugene Kontorovich (@EVKontorovich) October 22, 2018
Liberman says Israel has 'exhausted all options' on Gaza
Defense Minister Avigdor Liberman on Monday declared that Israel had exhausted efforts at reaching an arrangement with the Hamas terror group to end months of violence along the border with the Gaza Strip, and that the time had come for the cabinet to make a decision on military action.
Liberman's comments came days after a Palestinian rocket attack on Beersheba that drew a series of Israeli airstrikes on targets in Gaza. Egyptian and United Nations mediators have been working to reach an agreement between the two sides to calm the situation.
Speaking at the start of a Knesset Foreign Affairs and Defense Committee meeting, Liberman said the aim was to return the situation to the way it was before the end of March, when Palestinians in Gaza began weekly violent protests at the border.
"We have exhausted all of the options, and now it is time to make decisions," he said. "My position is very clear: We need to deliver a powerful blow to Hamas — that is the only way to get the situation back to the way it was before and to lower the level of violence to zero, or nearly zero.
"That needs to be a decision by the cabinet," Liberman continued. "I hope the cabinet will make the correct decisions. We have arrived at the point of no choice."
Watch – Aaron Klein: Iran Fingerprints on Gaza Terror Escalation
Iran may be influencing the Hamas terrorist organization to "light things up" in Gaza to deflect Israeli military attention away from countering the ongoing Iranian military presence in Syria, Breitbart Jerusalem chief Aaron Klein contended.
Klein made the comments during a panel discussion on Israel's i24NEWS.
Speaking on the news network's Spin Room program, hosted by Ami Kaufman, Klein stated:
I think Hamas is very nervous right now about the economic situation in the Gaza Strip. You've got Qatar pouring in fuel bypassing Hamas, bypassing the Palestinian Authority. And Hamas has to turn the anger of the Palestinian population again somebody and so they are trying to turn it against Israel.
And by the way I am also wondering if Iran is sort of hijacking what is going on in the Gaza Strip as well because they are very nervous right now in Syria. And it looks like they might be telling Hamas to light things up in Gaza.
Klein was speaking following a week of escalated attacks against Israel emanating from the Gaza Strip, including ramped up violent border riots, an increase in the number of incendiary devices being launched into Israel, the planting of an explosive device at the Israeli border fence, and the firing of two rockets toward central Israel. One rocket landed on an Israeli home in Beersheba, a city of 200,000, while a second rocket reportedly hit near the Tel Aviv area but fell into the sea.
Klein criticized the Israeli government for its willingness to continue negotiating a truce with Hamas while Israeli cities come under fire.
Ambassador David Friedman will now serve all of Jerusalem
On May 14, 2018, President Donald J. Trump moved the United States Embassy from Tel Aviv to Israel's eternal capital, Jerusalem. Now Trump has made another decision with tremendous courage and foresight: to merge the United States Consulate in Jerusalem with the new United States Embassy in Jerusalem.
As a member of the Trump Faith Initiative, I cannot praise this president enough on the incredible steps he has taken not only in Israel, but for the entire Middle East. The merging of the two entities will give US Ambassador to Israel David Friedman, who is the first United States Ambassador honored with the privilege to serve in Israel's eternal and undivided capital, the ability to serve in all of Jerusalem.
Unknown to most, the United States Consulate in Jerusalem has a long-standing reputation of working against the State of Israel, as well as against the status quo. The US Consulate is located in western Jerusalem, however, it serves Arabs who live in eastern Jerusalem and works directly under the US State Department, instead of rightfully under the American Ambassador to Israel. It is the US Ambassador, David Friedman, who works directly under the president of the United States and will ensure the continued strengthening of the US-Israel relationship.
This major move will once again affirm Israel and the Jewish people's connection to all of Jerusalem, a city that King David united and that has been the center of Jewish life for over 3,000 years. The merging of the two entities will also play an important role in the Trump administration's Middle East peace plan. As Prime Minister Benjamin Netanyahu has stated again and again: "A peace that is built on lies will crash on the rocks of Middle Eastern reality."
Thank you President Trump. You have once more recognized reality and made history in Jerusalem, the city of truth.
Watch – Aaron Klein to Australia: Ignore 'Arab Street' Myth and Move Embassy to Jerusalem
Australia should ignore critics warning against relocating its embassy from Tel Aviv to Jerusalem and instead make the move, argued Breitbart Jerusalem chief Aaron Klein.
Klein made the comments (video above) during a panel discussion on Israel's i24NEWS.
Amid reports that Australia is considering a change in its policy toward Jerusalem, some naysayers argued that such a move could ignite regional violence or impede peace talks.
Speaking on i24NEWS' Spin Room program, hosted by Ami Kaufman, Klein urged the Australian government to sidestep those critics:
This is the same argument that we heard against moving the American embassy to Jerusalem. What violence? We were talking here about the end of the world. The Arab street would revolt. It was largely silent. So first of all, let's not feed into this paranoia about the Arab street when it comes to moving embassies to Jerusalem.
And then second, the other argument is that this somehow impedes peace efforts. As if again the Palestinians haven't refused numerous statehood offers with a capital in Jerusalem. But actually it doesn't impede any effort because easily if the Palestinians accept a state, then America and others can open up an embassy or a consulate in the eastern sections of Jerusalem. And Australia has traditionally stood with American foreign policy and I think that they are doing that now, as well.
Last week, Prime Minister Benjamin Netanyahu's office confirmed in a statement that Australian Prime Minister Scott Morrison informed the Israeli leader during a phone call that his government is "weighing officially recognizing Jerusalem as the capital of Israel and moving the Australian embassy to Jerusalem."
Honest Reporting: Antisemitism: Judas Slur on Jewish Voters
An Australian by-election has taken on local, national and international significance as Australia's ruling Liberal party fought to hold its a one-seat majority in the parliament. (They didn't succeed.)
It is not for HonestReporting to take a public stance on the outcome of the Wentworth by-election. However, it is no secret that the Liberal candidate Dave Sharma, a former Australian ambassador to Israel, was and is a great friend of the country and the Jewish community.
By virtue of this and Wentworth's large number of Jewish constituents, a controversy broke out as Prime Minister Scott Morrison floated a trial balloon that he was "open" to moving the Australian embassy from Tel Aviv to Jerusalem. Given the timing, he was accused of trying to cynically buying Jewish votes through foreign policy.
Tony Walker
This is a legitimate debate to be had. But an opinion piece by award-winning journalist Tony Walker republished by the Australian Broadcasting Corporation (ABC), however, goes too far, leading off:
In the Gospel of Matthew 26:15, it took 30 pieces of silver for Judas Iscariot to betray Jesus. In modern Australian politics it has taken the prospect of a loss of a byelection for a political leader to opportunistically upend longstanding policy.
It's one thing for Walker to suggest that Jewish voters in Wentworth have been paid off for their vote. It's quite another to draw a parallel with the story of Judas and the 30 pieces of silver. When applied to Jews, this is a classic antisemitic trope.
Guardian cartoon smears Australian Jews as 'apartheid enthusiasts'
As we've noted in a series of Tweets, the Guardian has been obsessed with comments made by Australia's prime minister Scott Morrison expressing a willingness to consider moving Australia's embassy to Jerusalem. The remarks, made days before a by-election in the community of Wentworth, were interpreted by many as an appeal to the Jewish residents (who make of 13% of the district) to vote for the Liberal Party candidate David Sharma, Australia's former ambassador to Israel.
Over the course of three days, the Guardian went into full pro-Palestinian advocacy mode, publishing 15 articles and op-eds on Morrison's comments, some of which were borderline hysterical, focusing not only on predictable Palestinian criticism and the possible diplomatic fallout with Indonesia, but also on what editors seemed to believe would be the inevitable political upheaval and violence if the policy was enacted. The Guardian's predictions of calamity if Australia moved their embassy mirrored their alarmist predictions ahead of the US decision to move their embassy, prophecies of regional doom which, of course, didn't come true.
However, at the end of the day, Sharma lost the election, which resulted in the prime minister's party losing its razor-thin majority in the House of Representatives, presumably rendering the prime minister's Jerusalem comments moot.
But, Guardian contributors still weren't finished with vilifying the proposal. Their cartoonist 'First Dog on the Moon' published a graphic take on the fallout of the election titled 'Wentworth and the charred remains of the Morrison government's hopes and dreams'. Whilst most of the cartoon deals with Australian political issues unrelated to Morrison's embassy comments, it devoted a frame to the row, here:
Head of German Jewish community is not a Jew – report
The head of a German Jewish community has been reported to be, in fact, a non-Jew falsely claiming Jewish heritage.
Wolfgang Seibert, 71, has since 2003 been heading the Jewish community of Pinneberg, a town near Hamburg in northern Germany, and publicly identifies as a Reform Jew.
But family documents show that neither he nor his parents and grandparents are Jewish, and that he hasn't converted to Judaism, according to a report Friday by the German newspaper Der Spiegel, which called him a "scammer."
Research revealed that Seibert was born to Christian Protestant parents in Frankfurt and baptized at the age of three days, according to the report.
Soldier lightly injured in stabbing attack in Hebron; assailant shot dead
An Israeli soldier was lightly injured in an apparent stabbing attack in the West Bank city of Hebron on Monday morning, the army said.
The assailant was shot and subdued by the serviceman and other troops on the scene, according to the Israel Defense Forces.
"A terrorist tried to stab a soldier near the Tomb of the Patriarchs and lightly wounded him. The soldier and additional forces at the scene responded with live fire," the army said.
The soldier was a member of the Defense Ministry's liaison unit, known formally as the Coordinator of Government Activities in the Territories.
He was walking with an officer from COGAT's Hebron coordination office when he was attacked. After a brief struggle, the soldier distanced himself from the assailant and shot him.
Pictures from the scene that were posted to social media appeared to show the alleged stabber dead, his body covered by black plastic sheeting.
State files indictment against terrorist who murdered Ari Fuld
An indictment was filed on Monday against the terrorist who murdered Ari Fuld, on September 16, 2018, according to IDF Spokesperson's Unit.
Fuld,45, was stabbed in the back by 17 year-old Palestinian, Khalil Yusef Ali Jabarin, outside the Gush Etzion shopping center.
Mortally wounded, Fuld chased his Palestinian attacker, jumped over a short stone wall and shot him before collapsing. He was evacuated to Jerusalem's Shaare Zedek Medical Center where he succumbed to his wounds.
Jabarin, who was shot by Fuld and another armed civilian, was evacuated in moderate condition and fully conscious to Hadassah University Medical Center in Ein Kerem.
"If there is one word to describe my brother, it was a hero," Fuld's brother told mourners at the funeral.
National Union leader and Agriculture Minister Uri Ariel called the murder "a tremendous loss of a precious person, a hero who fought until his last breath to prevent other citizens from being harmed."'
Ari Fuld's Widow Sends Letter to Head of IDF Urging Demolition of Terrorist's Home
iriam Fuld, the widow of Ari Fuld who was murdered last month in a terrorist attack in Gush Etzion, sent a letter to the head of the IDF Central Command calling on him to demolish the home of the terrorist who murdered her husband.
"I have a simple question," wrote Fuld in a letter addressed to head of the IDF Central Command, Maj. Gen. Nadav Padan, "Why is the decision to demolish the home of the depraved terrorist being delayed?"
"It's important for me to emphasize," continued Fuld, "that the desire to advance the home demolition of the murderer does not stem from a place of revenge. Rather, this demand is intended to increase deterrence in order to save lives."
Fuld added: "Ari won't return to his family, but I know that he would act as I am, out of a desire to prevent even one more family from experiencing the same pain and suffering that we have."
Lt. Col. (res) Maurice Hirsch, former chief IDF prosecutor in Judea and Samaria, said that the delay is incomprehensible.
"In his last breath, Ari acted with extraordinary courage to protect other citizens from being killed," said Hirsch. "The family now expects for the security forces to act, like Ari, to protect the citizens of Israel against other murderers and increase deterrence by means of demolishing the terrorist's home."
Lawyer says top PA officials held by Israel suspected of kidnapping US citizen
Two top Palestinian officials arrested by Israeli forces over the weekend were held on suspicion helping abduct a Palestinian resident of Jerusalem, who was also a US citizen, their lawyers said on Sunday.
Israeli forces arrested Palestinian Authority Jerusalem Governor Adnan Ghaith and Jihad Faqih, the Jerusalem director of the PA General Intelligence Services, on Saturday, but declined to say why.
However, the two are suspected of having assisted in abducting a resident of Jerusalem two weeks ago, who has since been held by the Palestinian Authority in the West Bank, their lawyers told the Reuters news agency. Both men deny the charges.
Hadashot news reported that the man who had been abducted was wanted by the Palestinians for selling an Arab property in Jerusalem's Old City to Jewish investors.
The Palestinians frequently hand out the death penalty to those convicted of selling land to Israelis, though PA President Mahmoud Abbas has not authorized the implementation of such executions since his election in 2004.
Instead, he has imposed a sentence of hard labor for life on "anyone diverting, renting or selling land to an enemy state or one of its subjects."
PA condemns arrest of senior Palestinian officials by Israel
The Law for the Implementation of the Agreement on the Gaza Strip and the Jericho Area – Restriction on Activity – 1994 bans the PA from carrying out any type of activities within the area of Israel, including in east Jerusalem. The purpose of this law is to ensure compliance by the PA concerning the restriction of their activity, and to prevent political, governmental or similar activities within that area.
Last Friday, the Post revealed that PA security forces arrested a Palestinian-American citizen on suspicion of involvement in the sale of a house in the Old City of Jerusalem to a Jewish organization. A US official expressed concern over the arrest of the man and said the State Department was following up on the case with the PA. On Sunday, it was not clear whether the two senior officials, Geith and Fakih, were connected to the arrest of the Palestinian-American.
In recent weeks, the PA and the ruling Fatah faction have been investigating the sale of another Old City house to the Jewish organization, Ateret Cohanim. The Joudeh family, who owned the property, has denied selling the house to Ateret Cohanim. Documents presented by the family show that the house was originally sold to an Arab businessman from east Jerusalem last August.
PA and Fatah officials have described the real estate transaction as an act of "high treason." Palestinian religious authorities in east Jerusalem reaffirmed a fatwa (religious decree) banning Palestinians from selling property to Israelis. The PA government has formed a commission of inquiry in order to investigate the circumstances surrounding the sale of the house, which is located in the Muslim Quarter.
"The arrest of Geith and Fakih is a new crime against the Palestinian people," the PA government said in a statement. "It's also a crime against the Palestinian leadership and our eternal capital, the occupied Arab city of Jerusalem."
Yusef al-Mahmoud, spokesman for the PA government, accused Israel of seeking to "isolate Jerusalem from its natural surrounding" by arresting the two officials.
Arab Looters Damage Ancient Jewish Archaeological Site
A 2,000-year-old antiquities city near Afula were damaged by two antique robbers with a backhoe loader, according to the Israel Antiquities Authority Unit for the Prevention of Antiquities Robbery.
The excavation site of Horvat Devora, which has been identified as the biblical city of Dovrat and the Roman-era Jewish town of Davrita, was pillaged last week by looters.
Two Arab brothers in their 30s from the nearby town of Daburiyya are charged with destroying underground tunnels and displacing large ancient building blocks, including pieces of Hellenistic Period basalt grindstones, which were once used to grind flour.
Dovrat was a significant city during its day and a major hub for Jewish activity, with the site featuring the infrastructure of an ancient settlement, including water pits and graves.
The Nature and Parks Authority suspected looters when it detected damage to the site days prior to the discovery, putting Horvat Devora under surveillance.
Nir Distfeld, an IAA northern sector inspector, was quoted by Ynet as saying the "brutal, illegal excavations cause horrible damage to archaeological sites, and irreversibly hurt the historical research that concerns everyone's history." The site has apparently suffered repeated robbery attempts from Arabs from the same town.
"The damage is heartbreaking. Luckily, they were arrested before a greater loss was caused," Distfeld was quoted as saying. "It is important to note that excavating an archaeological site is a felony punishable by up to five years incarceration."
IDF says Hezbollah still on border illegally, posing as green NGO
The Israeli military on Monday accused the Lebanese Hezbollah terrorist group of conducting clandestine activities along the border with Israel under the guise of an environmental group known as "Green Without Borders."
The Israel Defense Forces made a similar claim in June 2017, identifying five observation posts owned by the non-governmental organization, which the army said were actually being used to carry out intelligence and reconnaissance work for the Iran-backed terror group.
"Now we are revealing a new position," said a senior official from the IDF Northern Command.
The alleged Hezbollah observation post was located in the Lebanese town of Aadaysit Marjaayoun, less than a kilometer from the border and from the Israeli community of Misgav Am, according to the officer, who spoke on condition of anonymity.
"We see them gathering intelligence on Israeli activities," the official told reporters.
The officer said the military believed that Hezbollah was using that information in order to prepare to commit attacks against Israeli military and civilian targets.
The senior official said the IDF had notified the peacekeeping United Nations Interim Force in Lebanon (UNIFIL) about the site and hoped it would inspect the observation post.
"We expect UNIFIL to surveil these positions and visit them. Until now, they haven't done so," he said.
UNIFIL did not immediately respond to a request for comment.
IDF Blog: Hezbollah's Fake Environmental Organization
"Green Without Borders" would be a great name for an environmental organization. Too bad Hezbollah made it up to disguise their terror activity along the Israel-Lebanon border.
Anticipating Hezbollah Clash, Israel Builds Barriers, Deploys Tanks on Lebanon Border
In recent weeks, residents of the Upper Galilee region have witnessed trucks unload countless mounds of sand and watched artificial hills slowly rise, with a tank or armored personnel carrier parked atop each one.
"The hills are being built close to the cement barrier the IDF has been building in recent months along the border," an area resident told Israel Hayom, referring to Israel's border with Lebanon. "Judging from what I've seen, they are being built opposite Hezbollah watchtowers in a manner that allows [Israeli soldiers] to see past the cement wall, into Lebanon."
"While they were building the [cement] barrier, I saw a tank overlooking the work, and now we see the same tank on the hill itself," he said.
However, defense officials told Israel Hayom that there was no connection between the location of Hezbollah's watchtowers and the location of the artificial hills where the tanks and APCs have been deployed.
According to one Israeli official, the purpose of the new positions is to give the IDF a field of vision beyond the cement barrier that has been built along the border in recent months.
The artificial sand hills are higher than the cement barrier, which is between and 6 to 8 meters (20 to 26 feet) tall.
The sand mounds are part of the army's broader efforts to erect obstacles along the Lebanese border.
Hezbollah sees Israel's empty threats in Gaza
While IDF Chief of Staff Gadi Eisenkot was in the Gaza Division on Friday to closely monitor the border fence riots, Fox News reported that American and other Western intelligence officials estimate Iran has recently increased the frequency of its advanced weapons deliveries to Hezbollah.
As far as Eisenkot is concerned, this is the real headache he leaves to his successor, who has not only yet to be announced, but will also not have enough time for on-the-job training. According to Fox News' report, the latest shipments included GPS components meant to upgrade rockets and turn them into precision-guided missiles. Senior officials told the TV network that one of the flights landed in Lebanon on Tuesday. The plane, a Boeing 747, first touched down in Damascus and then continued to Beirut.
Fox News' report follows another report that noted that "accuracy kits" meant for the long-range missiles the Iranians having in Lebanon, are smuggled on commercial passenger airplanes going directly to the Beirut airport, where they enjoy cooperation from local authorities. This is how Iran overcomes the main obstacle to arms shipments—the possibility they'll be attacked by Israeli aircraft, as has happened more than once in the past.
This modus operandi is consistent with the pressure Russia has been exerting on Iran in an effort to maintain the quiet in Syria since the Russian intelligence plane was shot down in the Latakia area over a month ago. But this is not enough for Hezbollah, as in addition to the GPS components the Shi'ite terror organization wants more long-range missiles as well as additional components to upgrade the accuracy of the existing missiles.
Amb. Nikki Haley: Iran's Use of Child Soldiers Is a Moral Outrage
U.S. UN Ambassador Nikki Haley told the UN Security Council on Thursday: Some in the international community still labor under the misimpression that the Iranian regime might be a responsible international actor, or might abide by the laws of a civilized society. Many, many things about the Iranian regime contradict this premise.
One of the most glaring is the continued use of children to fight and die in Iranian aggression abroad. The use of child soldiers is a moral outrage that every civilized nation rejects, while Iran celebrates it. In the Iran-Iraq War, 36,000 school-aged Iranian children were killed acting as human mine sweepers.
The Basij Resistance Force is a paramilitary force operating under Iran's Islamic Revolutionary Guard Corps. The Basij indoctrinate school children and provide combat training to children as young as 12 years old. These children are then coerced into fighting abroad for the IRGC. The Basij also targets Afghan immigrants in Iran, some as young as 14 years old, to fight in Syria. Last week, we identified the sources of the Basij's funding, and took action to cut them off from the global economy and financial system.
The sanctions the United States is leveling against Iran are broad and deep – and for good reason. Any company or individual that does business with this Iranian network is complicit in sending children to die on the battlefields of Syria and elsewhere.
How to Solve a Problem Like Mohammad bin Salman
When Saudi Arabia's Crown Prince Mohammad bin Salman (known as MbS) consolidated his power as successor to the throne and de-facto ruler, many in the West had high hopes for him. He allowed women to drive, initiated important economic reforms, cracked down on the export of an intolerant and fundamentalist brand of Islam, and tacitly realigned his country with Israel. But the kidnapping of the journalist Jamal Khashoggi and his death in custody—whether intentional or accidental—have, in Elliott Abrams' words, demonstrated the crown prince's "ignorance about the United States, impulsiveness, brutality, or all three." Abrams explains how the U.S. should respond:
[T]he image that MbS so carefully built has been smashed. Everyone has been reminded there is no modernizing of the Saudi government, just the sometimes praiseworthy and sometimes disgraceful efforts of one thirty-three-year-old man. Moreover, that man has decided that criticism is tantamount to treason. He has decided that to force the pace of change in the kingdom, as he believes he must, all opposition—whether it comes from within the royal family or from elements of broader Saudi society—must be crushed. No doubt he sees himself as an enlightened despot who must seize all the reins of power or see the brighter future slip away.
This cannot work, for us or for Saudi Arabia. That conclusion is based not only on sentiment or on moral revulsion at what was done to Jamal Khashoggi, whom I knew, but on a realist view of Riyadh. It would not be fair to say that the current Saudi arrangements inevitably led to the gruesome scene in the Saudi consulate in Istanbul, but that denouement was more a logical byproduct than an accident. . . .
MbS is today crown prince, deputy prime minister (the king always has the additional title of prime minister), defense minister, head of the Council for Economic and Development Affairs, head of the Council on Security and Political Affairs, and more. That arrangement is unprecedented for Saudi Arabia and is alien to every other Arab monarchy. . . . Whatever MbS loses in his ability to force through beneficial changes must be given up now, because unrestrained, unlimited power has too often been used badly.
French-Algerian Activist: In Five Years, the Smell of Zionists Will No Longer Be on This Earth
French-Algerian activist Yahia Gouasmi said that there is "no repentance" for Zionism or for Wahhabism and that Zionism would be "uprooted from the land of Palestine." "We believe that it will not take more than five years, and your smell will no longer be on this Earth," said Gouasmi, who is the founder of the Shiite Zahra Center and head of the Anti-Zionist Party of France. He made the remarks in an address posted on his YouTube channel on June 3, 2018.
We have lots of ideas, but we need more resources to be even more effective. Please donate today to help get the message out and to help defend Israel.
Hamas vehemently denies reports that it is moderating. Again.
by Ian in news
http://elderofziyon.blogspot.com/2016/07/hamas-vehemently-denies-reports-that-it.html For many years, reporters have been fooling themselves into interpreting Hamas statements as if the group is willing to accept Israel under specific circumstances, and every time Hamas explicitly denies any such report. The [...]

redpajama_set_name: RedPajamaCommonCrawl


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Bryan Singer dropped from Red Sonja film
Bryan Singer has been fired from Millennium Films' Red Sonja movie
Bryan Singer has been dropped from the Red Sonja film that's currently in production at Millennium Films, according to THR, but not for the reason you may think.
Singer, who was set to direct the film, was fired by the studio not because of the reports of him sexually assaulting underaged boys but because the production company was finding it impossible to secure a US distributor with Singer involved.
The film is reportedly currently on hold, but it's unknown whether or not it will get a new director any time soon.
In an interview with THR, original Red Sonja actress from the 1985 film Brigitte Nielsen said she'd love for the new film to hire a female director.
"But why don't they go with a great female director? Like Susanne Bier, a great Danish director? That would be fantastic!" she said. "And she would put me in Red Sonja because I need to be in there! Or you could do Patty Jenkins! She's an incredible director!
"This is a huge female character, and I can see a fantastic female director. Let me have my first project as a director! I'll do it! (Laughs) I'm kidding. But a female director wouldn't be a bad idea if Singer is eventually off the project for whatever is going to happen. I'm not one to say."
The character of Red Sonja was created by writer Roy Thomas and artist Barry Windsor-Smith for Marvel Comics in 1973, and made her first appearance in Conan The Barbarian #23. She was partially based on Robert E Howard's characters Red Sonya of Rogatino and Dark Agnes de Chastillon. She is a sword-master in peak human physical condition and a martial arts expert, with much knowledge and experience of fighting the supernatural, and is famous for her bikini armour made of scale mail.
Red Sonja doesn't yet have a release date. Get all the latest sci-fi news with every issue of SciFiNow.
Red Sonja film hires Jill Soloway to write and direct Conan The Barbarian TV series coming from Amazon DC's Harley Quinn Birds Of Prey film to be directed by Cathy Yan Dexter Fletcher to direct Renfield film based on Dracula's henchman Sony and Kay Cannon working on a Cinderella reimagining starring Camila Cabello
Tags: Red Sonja


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As the Senior Account Executive, you have a firm understanding of strategy from concise and insightful creative briefs to media alternatives, and will work directly with clients and our internal teams to develop, oversee and assist with the implementation, budgeting and forecasting of client initiatives. You will lead the go to market activity and effectively execute integrated communications plans, oversee tracking and completion of client status reports, generate creative solutions to meet client needs, maintain strong client and internal cross-functioning relationships, and identify resources as needed. You will be vigilant in identifying upselling opportunities while looking after the best interests of the agency. You are someone who writes with clarity and expressive technique. You are always proactive, and don't wait for orders or for the phone to ring. When presenting agency work and ideas, you communicate with confidence and a diplomatic authority, with preparedness to defend agency work where/when appropriate, and have the ability to build client and internal stakeholder trust organically.


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Hans Stockmar (* 17. März 1890 in Sydney (Australien); † 16. Januar 1961 in Hamburg) war ein deutsch-britischer Anthroposoph und Unternehmer.

Familie
Hans Stockmar wurde als Hans Maximillian Alexander Bruno Beheim-Schwarzbach als erster Sohn des Würzburger Augenarztes Bruno Beheim-Schwarzbach und dessen Ehefrau Carola Beheim-Schwarzbach, geb. Stockmar, († 1907) in Australien geboren. Seit 1912 nannte er sich nach dem mütterlichen Geburtsnamen Hans Stockmar. Die Eltern waren deutscher Herkunft, hatten aber die britische Staatsbürgerschaft angenommen. Sein Vater entstammte der Patrizierfamilie Behaim von Schwarzbach.

Sein Bruder war der Schriftsteller und Schachspieler Martin Beheim-Schwarzbach (1900–1985). Im Jahr 1904 ließen sich die Eltern scheiden: Das Kind Maximilian blieb beim Vater, die Mutter zog mit dem Kind Martin nach Hamburg. Dort heiratete sie den verwitweten Großkaufmann Eduard Hernsheim († 1917). Carola Hernsheim starb 1907, und der Witwer heiratete deren Schwester.

Leben
Wegen der Weltreisen seines Vaters absolvierte das Kind seine Schulbildung an unterschiedlichen Orten. Nach der Heirat mit der Schauspielerin Vilma Regling wanderte das junge Ehepaar 1912 nach Neuseeland aus, wo es zur Namensänderung in Hans Stockmar kam. In Neuseeland wurden die Kinder Heimdal, Anselm und Rahel geboren. Um ihnen den Schulbesuch in Deutschland möglich zu machen, ging die Familie 1921 wieder zurück nach Deutschland. Die beiden jüngeren Kinder hatten die Gelegenheit, die neu gegründete Waldorfschule in Hamburg-Wandsbek zu besuchen.

In Neuseeland hatte Hans Stockmar eine Gärtnerei sowie eine Imkerei aufbauen können. Nach der Rückkehr gründete Hans Stockmar im Jahr 1922 in Kaltenkirchen die gleichnamige Bienenwachsschmelze Hans Stockmar zur Herstellung von Mittelwänden für den Bienenstock sowie von Bienenwachskerzen. Weil das Unternehmen nur einen geringen Umsatz erwirtschaftete, arbeitete Hans Stockmar von 1921 bis 1931 in den Wintermonaten als Steward auf den Schiffen internationaler Linien. Dann erwirtschaftete der Betrieb schließlich ausreichende Erträge.

Während des nationalsozialistischen Regimes unterhielt Hans Stockmar einen intensiven Kontakt zu seinem ehemaligen jüdischen Mitarbeiter Joseph Gelbart († 1942), der ins Warschauer Ghetto deportiert war. Im Jahr 2002 erhielt Hans Stockmar posthum vom israelischen Staat den Ehrentitel Gerechter unter den Völkern.

Hans Stockmar befasste sich seit seiner neuseeländischen Zeit mit der Anthroposophie, insbesondere mit dem Werk Rudolf Steiners. Sein Haus in Kaltenkirchen entwickelte er zu einem kulturellen Zentrum für anthroposophische Themen.

Weblinks
 Stephan Stockmar (Forschungsstelle Kulturimpuls): Hans Stockmar.

Unternehmer (20. Jahrhundert)
Deutscher
Geboren 1890
Gestorben 1961
Mann

redpajama_set_name: RedPajamaWikipedia


"We met Shawn about 2 1/2 years ago at a mutual friends house and as we were having conversations with him we mentioned that we were "thinking" about buying a house. Certainly at that time the "thinking" part really had no clue as to where we wanted to go but we were in a rental home and we knew that we wanted something more permanent. Shawn gave us his contact information and Barb and I really filed it for awhile until we got serious about looking for a home.
When we first called Shawn, we explained to him what we were interested in and what our criteria was. Obviously that was an open door for him to take us everywhere. What we liked immediately with Shawn was his patience and understanding of our needs and not just selling a home to make a commission. This process took somewhere in the midst of about a 3 months before we made a final decision. As we were approaching the final step of putting an offer on a home, Shawn called us and gave us bad news that the home already had an offer on it. We were about to give up when he basically said let's look at one more that "I think you will like." We walked in and immediately fell in love with the home that we own today.
To sum it up, Shawn is not your typical realtor. He listens very effectively, he is detailed in his evaluations of looking at homes based on your needs and quite frankly he talks to you as if he were buying a home for himself. Selling a home for Shawn is not because of a commission its because he wants you to be happy in the home and he brings a lot of personal character into his selling. His knowledge is impeccable about areas that are good to look at, he does his homework and let's you know exactly what you can expect. More importantly Shawn is a "non- pressure" realtor, who wants your business because of his relationship that he develops with you. We met Shawn in a small get together and because of his outgoing personality we have developed a very good friendship, not just another realtor."


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HOUSTON – The United Steelworkers (USW) yesteday said that Houston area oil workers will sponsor a noon rally at Shell headquarters on Friday, Feb. 6, to show management that union members are united in their drive for a fair contract that improves safety throughout the industry.
Union members began a strike at nine U.S. refineries and chemical plants in California, Kentucky, Texas, and Washington on Feb. 1, after their previous contract expired and industry negotiators, represented by Shell, failed to address serious concerns raised by the USW regarding the health and safety of workers and their communities.
USW members account for about 64 percent of the country's oil refining capacity, and more locations could soon join the strike if necessary.
On Saturday, the union will hold a National Day of Action at 65 oil refineries, while steelworkers at almost 200 other facilities across the country, including oil terminals, pipelines and petrochemical plants, will also participate in solidarity actions.


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Tag Archives: David H. Keller
SCIENCE FICTION OF THE THIRTIES edited by Damon Knight
TITLE: SCIENCE FICTION OF THE THIRTIES
EDITED BY: Damon Knight
SUB-CATEGORY: Anthology
PUBLISHER: The Bobbs-Merrill Company, Inc., Indianapolis/New York, 1975
FORMAT: Hardback, 1st Edition, 464 pages
Foreword by Damon Knight
"Out Around Rigel" by Robert H. Wilson (1931)
"The Fifth-Dimension Catapult" by Murray Leinster (1931)
"Into the Meteorite Orbit" by Frank K. Kelly (1933)
"The Battery of Hate" by John W. Campbell, Jr. (1933)
"The Wall" by Howard W. Graham, Ph.D. (1934)
"The Lost Language" by David H. Keller, M.D. (1934)
"The Last Men" by Frank Belknap Long, Jr. (1934)
"The Other" by Howard W. Graham, Ph.D. (1934)
"The Mad Moon" by Stanley G. Weinbaum (1935)
"Davey Jones' Ambassador" by Raymond Z. Gallun (1935)
"Alas, All Thinking" by Harry Bates (1935)
"The Time Decelerator" by A. Macfadyen, Jr. (1936)
"The Council of Drones" by W. K. Sonnemann (1936)
"Seeker of Tomorrow" by Eric Frank Russell and Leslie T. Johnson (1937)
"Hyperpilosity" by L. Sprague de Camp (1938)
"Pithecanthropus Rejectus" by Manly W. Wellman (1938)
"The Merman" by L. Sprague de Camp (1938)
"The Day is Done" by Lester del Rey (1939)
What SF Master Damon Knight has done for Science Fiction of the Thirties is to plough his way through hundreds of classic "pulps" from the 30's, mining them for a few of the forgotten gems from that era, and picking out the best of them for this anthology. He has reappraised the best of the tales from the 1930s SF magazines, with the added condition that his choices are stories which have rarely, some of them never, been published before in SF anthologies. And it's a real thrill to read these stories, particularly for a jaded old fan like me who thought he'd read all the good old stuff worth reading.
Reading the short but fascinating Foreword to this anthology, we come to understand that Knight had been a life-long critic of the stories in the pulps, but had undergone a recent change of heart. Sturgeon's Law ("Ninety Percent of Everything is Crud") applies to the pulps just as much as it does to everything else, and it is the ten percent of stories which are not crud which make it worth persevering, and wading through the crap, to find the diamonds in the rough. And these stories are all good 'uns. Damon Knight, former unrelenting critic of the "pulps", is a hard taskmaster, and his standards are VERY high.
So, given that I've read a LOT of vintage SF, how has he done? The good news is that I'm totally unfamiliar with at least six of the authors in this anthology. The rest of them are names that I know, but the real surprise is that I have never read most of these stories before. I'm familiar with only THREE out of the eighteen stories – Weinbaum's "The Mad Moon", Campbell's "The Battery of Hate" and Bates' "Alas, All Thinking" (all of which I read many, many years ago) – which is a pretty amazing strike rate for Knight and the stories that he has chosen here. He has really come up with the goods, producing an anthology of stories that few SF readers will have seen before.
Most modern SF anthologies showcasing stories from "the old days" have long since started to reprint the same classic stories over and over again, so an avid SF fan would very likely have read most of them before. As good as many classic SF stories are, it becomes a bit tiring and disheartening to see them in every other anthology – "The Cold Equations" and "It's a Good Life" are two examples of classic SF stories that come to mind. I have these two in so many old anthologies that I could scream every time I see them in yet another. I love these stories to bits, but too much of a good thing, etc…
Which raises the question: if Damon Knight could find these forgotten gems, surely there are many, many more in those SF magazines, just waiting for some adventurous researcher and editor to find them? And now that Damon has sadly passed on from us, to that great everlasting Science Fiction Convention in the Sky, who is willing to step into his giant shoes and continue to unearth these hidden treasures of the past? Or do hardcore fans like me have to continue ponying up exorbitant amounts of money for the old SF magazines or rare, out-of-print anthologies from the dim and distant past, in order to unearth more forgotten SF gems?
SF editors need to start using a bit of imagination and initiative, as in "Great story, but it's been published a zillion times before. How's about something that hasn't been published before?". I know that great editors of the past (and present) have produced many excellent anthologies of vintage SF. Editors like Groff Conklin, Terry Carr, Isaac Asimov, Martin H. Greenberg, Gardner Dozois, Brian Aldiss, Mike Ashley, and many others have produced some amazing anthologies over the years. But many of the classic editors/anthologists have now sadly passed on, and we have a dire need for newer editors to come forward and take up the gauntlet, to continue the great work that Damon Knight and the other great editors of the past have done to unearth the forgotten SF treasures of the 1920s, 1930s, 1940s and 1950s. Sure, I'd be the first to say that we need new authors producing great new SF. But we should also never, EVER forget the old masters.
So what's my verdict of Science Fiction of the Thirties? Overall, I think this is an excellent anthology. Taking into account that these are NOT modern literary SF masterpieces, and that the stories are 1930s pulp SF tales, churned out at a few cents per word, it's amazing that ANY of them were any good. But some were real beauts. Even for as low grade a market as the "pulps", many talented writers took extreme pride and joy in their work, and went way beyond the line of duty, producing something much more than the miserly word rates they were being paid could ever merit. Damon Knight has uncovered a few of those forgotten gems for us and put them together in this very nice anthology. For someone like myself, who is a huge fan of finding good old SF stories that I haven't read before, this type of book is just right up my alley.
I wish there were a few more volumes of anthologies containing similarly rare old SF magazine stories out there. Here's hoping that someone will continue on with the good work of finding classic stories from the "pulps" that we haven't read before. I, for one, will be eagerly watching out for more.
Posted in SF Anthologies
Tagged A. Macfadyen Jr, Brian W. Aldiss, David H. Keller, Eric Frank Russell, Frank Belknap Long, Frank K. Kelly, Gardner Dozois, Groff Conklin, Harry Bates, Howard W. Graham, Isaac Asimov, John W. Campbell Jr, L. Sprague de Camp, Leslie T. Johnson, Lester del Rey, Manly Wade Wellman, Martin H. Greenberg, Mike Ashley, Murray Leinster, Raymond Z. Gallun, Robert H. Wilson, Stanley G. Weinbaum, Terry Carr, The Bobbs-Merrill Company Inc, W. K. Sonnemann
BEACHHEADS IN SPACE edited by August Derleth
TITLE: BEACHHEADS IN SPACE
EDITED BY: August Derleth
CATEGORY: Anthology
SUB-CATEGORY: Short Fiction
FORMAT: Hardback, 224 pages
PUBLISHER: Weidenfeld & Nicolson, London, 1954 (Originally published in the US in 1952 by Pellegrini & Cudahy).
That's the various general details, here's a listing of the contents:
"Beachhead" by Clifford D. Simak (1951)
"The Years Draw Nigh" by Lester del Rey (1951)
"Metamorphosite" by Eric Frank Russell (1946)
"Breeds There a Man…?" by Isaac Asimov (1951)
"And the Walls Came Tumbling Down" by John Wyndham (1951)
"The Blinding Shadows" by Donald Wandrei (1934)
"The Metamorphosis of Earth" by Clark Ashton Smith (1951)
This is an interesting old anthology, edited by another of my favourite SF anthologists, August Derleth. The theme of this anthology, according to the book's jacket blurb, is "invasion from another world, or counter-attack from Earth against the planets".
I haven't read this one in many years, maybe twenty-five years or more, but I remember that it was a favourite of mine way back in the day, and it still has a special place on my bookshelves. Obviously my memories of the individual stories are vague after all this time, and I don't remember all of them clearly, and a couple of them not at all. But the ones that I do recall really liking are Clifford D. Simak's very clever short story "Beachhead" (AKA "You'll Never Go Home Again!", first published in Fantastic Adventures, July 1951), Eric Frank Russell's excellent novella "Metamorphosite", (from Astounding, December 1946), and Clark Ashton Smith's scary and unusual alien invasion SF/Horror novelette "The Metamorphosis of Earth" (Weird Tales, September 1951).
I also remember liking Lester del Rey's "The Years Draw Nigh" and Isaac Asimov's "Breeds There a Man…?", although for some reason I remember a lot less about them than I do about the Russell, Simak and Smith stories. I don't recall anything at all about the Wyndham and Wandrei stories. I'm surprised about not remembering the Wyndham story, as I'm usually a big fan of his writing.
But as good as my recollections are of the Simak and Smith stories, the stand-out story for me in this anthology has always been Eric Frank Russell's classic "Metamorphosite", which I recall having a huge impact on me back when I was a young guy in my twenties. I don't think this story is in any of my other anthologies (and I have zillions of the darned things!), so I reckon it hasn't been reprinted very often. It's far, far too many years since I last read it, and indeed this entire anthology, so it's long overdue for a re-read. I've already started on the Simak story, and, so far, it's at least as good as I remember it, if not better. If the rest of the stories hold up as well as this one is doing, I'm going to really enjoy reading this anthology again.
Please take note that this is the 1954 UK edition, which is different from the original 1952 US hardcover edition, published by Pellegrini & Cudahy. Apparently all editions aside from the original hardcover edition have been "butchered" in some way, missing stories, etc. This UK edition is missing the Introduction and seven of the stories from the US edition. Also note that John Wyndham has two stories in the original US edition, one under his usual John Wyndham pseudonym, and the other as John Benyon.
Here is the full Contents Listing of the original 1952 US edition:
Introduction by August Derleth
"The Star" by David H. Keller, M.D.
"The Man from Outside" by Jack Williamson
"Beachhead" by Clifford D. Simak
"The Years Draw Nigh" by Lester del Rey
"Metamorphosite" by Eric Frank Russell
"The Ordeal of Professor Klein" by L. Sprague de Camp
"Repetition" by A. E. van Vogt
"Breeds There a Man…?" by Isaac Asimov
"Meteor" by John Beynon
"And the Walls Came Tumbling Down" by John Wyndham
"Blinding Shadows" by Donald Wandrei
"The Metamorphosis of Earth" by Clark Ashton Smith
"The Ambassadors from Venus" by Kendell F. Crossen
"To People a New World" by Nelson S. Bond
For lovers of old-style, classic SF short fiction, this anthology would be right up their alley. If you can actually find it, that is. As it's such an old book, it's obviously long out of print, and you'll have to hunt through used book stores to find this anthology. But it'll be well worth the trouble it takes to find it, as are any other anthologies edited by August Derleth.
After all these years, I think I'll actually make a major effort to get off my butt and track down the longer original US hardcover edition, which I didn't even realize was different/longer until I recently read the Wikipedia entry on the anthology.
Highly recommended, particularly the original US hardcover edition.
Tagged A. E. van Vogt, Astounding Science Fiction, August Derleth, Clark Ashton Smith, Clifford D. Simak, David H. Keller, Donald Wandrei, Eric Frank Russell, Fantastic Adventures, Interplanetary Invasion, Isaac Asimov, Jack Williamson, John Wyndham, Kendell F. Crossen, L. Sprague de Camp, Lester del Rey, Nelson S. Bond, Pellegrini & Cudahy, Weidenfeld & Nicolson, Weird Tales