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Reprogramming Stem Cells May Suppress Cancer after Radiotherapy

By MedImaging International staff writers
Posted on 27 Jan 2015

The body has developed strategies of purging defective stem cells. A new study has revealed that one of these ways is a “program” that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever.

Radiation makes a stem cell lose its “stemness,” which makes sense because damaged stem cells do not need to hang around to pump out damaged cells. Moreover, the research, conducted by University of Colorado (CU) Cancer Center (Aurora, USA) scientists, and published online December 27, 2014, in the journal Stem Cells, demonstrated that this same protection of “programmed mediocrity” that rids stem cells damaged by radiation allows blood cancers to grow in instances when the total body is irradiated. Furthermore, by reprogramming this defense, cancer may be prevented in the aftermath of full body radiation. “The body didn’t evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA,” said James DeGregori, PhD, investigator at the CU Cancer Center, professor of biochemistry and molecular genetics at the CU School of Medicine, and the article’s senior author.

Dr. DeGregori, doctoral student Courtney Fleenor, and colleagues examined the effects of full body radiation on the blood stem cells of mice. In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. Only, while most obeyed this instruction, a few did not. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their “stemness.” Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it's not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation. “It’s about evolution driven by natural selection,” Dr. DeGregori noted. “In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. But when radiation reduces the heath and robustness of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over.”

These studies do not only clarify why radiation makes hematopoietic stem cells (HSCs) differentiate; they also show that by activating a stem cell maintenance pathway, we can keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act “stemmy” again—restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.

When Drs. DeGregori, Fleenor and colleagues triggered NOTCH in earlier irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their health restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.

“If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs,” Dr. DeGregori stated, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their ‘programmed mediocrity’ [increased differentiation] and even HSC with cancer-causing mutations. “But there’s also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation.”

Related Links:
University of Colorado Cancer Center

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60 (151.8726348877): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

61 (!!!!! 8520.8415985107): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (!!!!! 1461.9827270508): SELECT fid FROM jos_deeppockets WHERE id=294756899 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294756899 AND published='1' LIMIT 1

63 (!!!!! 3964.1857147217): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=211 ORDER BY `ordering`

64 (106.0962677002): select jos_twitters.link from jos_twitters where cat=10

65 (30.040740966797): select jos_facebook.link from jos_facebook where cat=10

66 (34.093856811523): select jos_google_plus.link from jos_google_plus where cat=10

67 (29.087066650391): select jos_linkedin.link from jos_linkedin where cat=10

68 (35.04753112793): SELECT fid FROM jos_deeppockets WHERE id=294756899 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294756899 AND published='1' LIMIT 1

69 (48.160552978516): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=211 ORDER BY `ordering`

70 (!!!!! 3031.9690704346): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (797.03330993652): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (84.161758422852): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (504.0168762207): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (134.94491577148): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (128.98445129395): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (130.89179992676): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (131.13021850586): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (29.802322387695): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (132.08389282227): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (!!!!! 4616.0221099854): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (43.869018554688): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (36.001205444336): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (524.04403686523): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (144.00482177734): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (135.89859008789): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (146.86584472656): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (159.97886657715): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (!!!!! 3901.9584655762): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (504.0168762207): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (931.0245513916): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

105 (82.015991210938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

106 (!!!!! 1637.9356384277): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (746.9654083252): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (396.0132598877): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

109 (558.13789367676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

110 (!!!!! 1053.0948638916): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (759.12475585938): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (!!!!! 2359.8670959473): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (!!!!! 1348.9723205566): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (!!!!! 1127.0046234131): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

115 (130.89179992676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

116 (684.02290344238): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

117 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

118 (!!!!! 3283.0238342285): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

119 (!!!!! 1001.1196136475): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

120 (699.99694824219): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

121 (329.97131347656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

122 (530.00450134277): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 67847.967147827): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

124 (!!!!! 8267.879486084): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756899 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756899 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 43991.088867188): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (!!!!! 7642.0307159424): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (!!!!! 8133.8882446289): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

128 (!!!!! 7675.1708984375): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

129 (!!!!! 7518.0530548096): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

130 (!!!!! 7889.0323638916): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

131 (!!!!! 7987.9760742188): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

132 (!!!!! 7859.9452972412): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

133 (!!!!! 7023.811340332): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

134 (684.02290344238): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

135 (387.90702819824): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (!!!!! 1511.0969543457): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (!!!!! 8943.0809020996): SELECT name FROM jos_deeppockets WHERE id=211

138 (!!!!! 2138.1378173828): SELECT name FROM jos_deeppockets WHERE id=211

139 (!!!!! 1156.0916900635): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (!!!!! 6903.1715393066): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (!!!!! 5047.082901001): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

142 (468.96934509277): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

143 (!!!!! 26821.136474609): TRUNCATE TABLE jos_trademed_module

144 (420.80879211426): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (200.03318786621): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294756899 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (925.06408691406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (!!!!! 7225.9902954102): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (!!!!! 1360.8932495117): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

149 (479.93659973145): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

150 (!!!!! 1666.0690307617): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

151 (412.94097900391): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

152 (150.20370483398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

153 (262.97569274902): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756899 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756899 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (32.901763916016): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)

155 (242.94853210449): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)

156 (!!!!! 4006.8626403809): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (722.88513183594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

158 (881.91032409668): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756899 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756899 AND published='1' LIMIT 1

159 (82.969665527344): select jos_twitters.link from jos_twitters where cat=10

160 (48.160552978516): select jos_facebook.link from jos_facebook where cat=10

161 (39.815902709961): select jos_google_plus.link from jos_google_plus where cat=10

162 (!!!!! 10592.222213745): select jos_linkedin.link from jos_linkedin where cat=10

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