Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation
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{"title"=>"Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation", "type"=>"journal", "authors"=>[{"first_name"=>"Takashi", "last_name"=>"Koyama", "scopus_author_id"=>"55223480500"}, {"first_name"=>"Christen K.", "last_name"=>"Mirth", "scopus_author_id"=>"8919567100"}], "year"=>2016, "source"=>"PLoS Biology", "identifiers"=>{"issn"=>"15457885", "scopus"=>"2-s2.0-84959570201", "pui"=>"608714030", "doi"=>"10.1371/journal.pbio.1002392", "isbn"=>"10.1371/journal.pbio.1002392", "sgr"=>"84959570201", "pmid"=>"26928023"}, "id"=>"cf670aee-8df2-3ddc-bd7c-a873b411c46c", "abstract"=>"In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size.", "link"=>"http://www.mendeley.com/research/growthblocking-peptides-nutritionsensitive-signals-insulin-secretion-body-size-regulation", "reader_count"=>70, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>16, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>1, "Student > Master"=>11, "Student > Bachelor"=>10, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>16, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>1, "Student > Master"=>11, "Student > Bachelor"=>10, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>17, "Agricultural and Biological Sciences"=>43, "Medicine and Dentistry"=>2, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>43}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Japan"=>2, "Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4785772"], "description"=>"<p><b>(A, B)</b> Culturing wild-type brains with conditioned media from GBP1 and GBP2 expressing cells induces low level of ILP2 (A) and ILP5 (B) accumulation in the insulin-producing cells. To obtain brains, w1118 larvae staged at the onset of the L3 were fed on normal food for 12 h followed by 12 h incubation on 1% non-nutritive agar to induce strong ILP accumulation. To make conditioned media, an equal amount of Actin Gal4 plasmid and either UAS <i>gbp1</i>, UAS <i>gbp2</i>, or UAS <i>egfp</i> plasmid were transfected into the <i>Drosophila</i> SL2/DL2 cell line. Forty-eight hours after transfection, the media were centrifuged and the supernatant was diluted with culture medium to 100%, 50% and 25% the original concentrations. The scale bars are 20 μm. <b>(C, D)</b> Culturing wild-type brains with conditioned media from GBP1 and GBP2 expressing cells decreases the densities of ILP2 (C) and ILP5 (D) signals in the insulin-producing cells. We standardized the densities of ILPs by fixing the values from GFP 100% to 1. <i>n</i> = 16–27 for both ILP2 and ILP5. <b>(E, F)</b> Co-culturing wild-type brains with fat bodies from wild-type, but not from <i>gbp1</i>, <i>gbp2 ex67</i>, larvae induces low levels of ILP2 (E) and ILP5 (F) accumulation in the insulin-producing cells. The brains were obtained as above. The fat bodies were obtained as described in the Materials and Methods. <b>(G, H)</b> Co-culturing wild-type brains with fat bodies from wild-type, but not from <i>gbp1</i>, <i>gbp2 ex67</i>, larvae decreases the densities of ILP2 (G) and ILP5 (H) signals in the insulin-producing cells. We standardized the densities of ILPs by fixing the values from the “no fat body” treatment (culturing with a plain medium) to 1. <i>n</i> = 12–22 for both ILP2 and ILP5. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079360, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g008", "stats"=>{"downloads"=>6, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Both_GBP1_and_GBP2_are_secreted_from_the_fat_body_and_directly_act_on_the_brain_to_induce_ILP2_and_ILP5_secretion_/3079360", "title"=>"Both GBP1 and GBP2 are secreted from the fat body and directly act on the brain to induce ILP2 and ILP5 secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785721"], "description"=>"<p><b>(A, B)</b> Overexpressing both GBP1 and GBP2 partially rescues body size reduction in <i>gbp1</i>, <i>gbp2 ex67</i> mutant females (A) and males (B) at 22°C. <i>n</i> = 51–52 for A and <i>n</i> = 54–65 for B. <b>(C)</b> Overexpressing both GBP1 and GBP2 partially increases growth rate in <i>gbp1</i>, <i>gbp2 ex67</i> mutant larvae. <i>n</i> = 14–20/time point. <b>(D)</b> Overexpressing both GBP1 and GBP2 partially rescues the duration of the L3 in <i>gbp1</i>, <i>gbp2 ex67</i> mutant larvae. <i>n</i> = 111–119. <b>(E, F)</b> Overexpressing both GBP1 and GBP2 reduces ILP2 (E) and ILP5 (F) accumulation in the insulin-producing cells of <i>gbp1</i>, <i>gbp2 ex67</i> mutant larvae. Larvae were staged at the onset of the L3, and then fed on normal food for 24 h. The insulin-producing cells were immunostained using an anti-ILP2 antibody and an anti-ILP5 antibody. <b>(G, H)</b> Overexpressing both GBP1 and GBP2 reduces the densities of ILP2 (G) and ILP5 (H) signals in the insulin-producing cells. The densities of ILP2 and ILP5 were quantified using ImageJ. We standardized the densities of ILPs by fixing the values from <i>C7</i>>GFP in the <i>gbp1</i>, <i>gbp2 ex67</i> mutant background to 1. <i>n</i> = 30–60. <b>(I)</b> Overexpressing both GBP1 and GBP2 reduces FRE-luciferase activity in the entire body of <i>gbp1</i>, <i>gbp2 ex67</i> mutant larvae. <i>n</i> = 5. Two copies of UAS transgenes were expressed using the <i>C7</i> Gal4 driver. For the wild-type control, we overexpressed two copies of UAS GFP using the <i>C7</i> Gal4 driver. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). Growth rate was analyzed by ANCOVA and post hoc comparisons of the slopes. The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079312, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Overexpressing_GBP1_and_GBP2_in_the_fat_body_rescues_body_size_in_i_gbp1_i_i_gbp2_ex67_i_null_mutant_larvae_/3079312", "title"=>"Overexpressing GBP1 and GBP2 in the fat body rescues body size in <i>gbp1</i>, <i>gbp2 ex67</i> null mutant larvae.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785646"], "description"=>"<p><b>(A, B)</b> Knocking down GBP1 and GBP2 increases ILP2 (A) and ILP5 (B) accumulation in the insulin-producing cells. The scale bars are 20 μm. <b>(C, D)</b> Knocking down GBP1 and GBP2 increases the densities of ILP2 (C) and ILP5 (D) signals in the insulin-producing cells. We standardized the densities of ILPs by fixing the values from <i>C7</i>>2xGFP to 1. <i>n</i> = 16–27 for both ILP2 and ILP5. <b>(E, F)</b> The <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows increased ILP2 (E) and ILP5 (F) accumulation in the insulin-producing cells. The scale bars are 20 μm. <b>(G, H)</b> The <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows increased densities of ILP2 (G) and ILP5 (H) signals in the insulin-producing cells. We standardized the densities of ILPs by fixing the values from w1118 larvae to 1. <i>n</i> = 34–41 for both ILP2 and ILP5. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079237, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/GBP1_and_GBP2_regulate_ILP2_and_ILP5_secretion_/3079237", "title"=>"GBP1 and GBP2 regulate ILP2 and ILP5 secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785688"], "description"=>"<p><b>(A)</b> Concentration of circulating ILP2 is reduced in the <i>gbp1</i>, <i>gbp2 ex67</i> mutant. After SDS-PAGE, the gel was cut and upper half was stained with Coomassie Brilliant Blue (CBB) and putative larval serum protein 1α, β and γ proteins (90–100 kDa) were shown as a loading control. The lower half was used for ILP2 staining. (<b>B</b>) ILP2 signal density was quantified from three biologically independent experiments against putative larval serum protein 1α, β and γ proteins. We standardized the densities of all three proteins by fixing the values from w1118 to 1. <b>(C)</b> Knocking down GBP1 and GBP2 in the fat body shows reduced pAKT in the wing discs. AKT and Histone H3 were used as loading controls. (<b>D, E</b>) pAKT signal density was quantified from three biologically independent experiments against Histone H3 (D) and AKT (E). We standardized the densities of all three proteins by fixing the values from <i>C7</i>>2xGFP to 1. <b>(F)</b> The <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows reduced pAKT in the wing discs. AKT and Histone H3 were used as loading controls. (<b>G, H</b>) pAKT signal density was quantified from three biologically independent experiments against Histone H3 (G) and AKT (H). We standardized the densities of all three proteins by fixing the values from w1118 to 1. <b>(I)</b> Knocking down GBP1 and GBP2 increases FRE-luciferase activity in the entire body. Larvae were staged at the onset of the L3, and fed on normal food for 24 h. For the luciferase assay, we used the entire bodies of five larvae. We quantified five replicates for each genotype. <b>(J)</b> The <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows increased FRE-luciferase activity in the entire body. We quantified five replicates for each genotype. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079273, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/GBP1_and_GBP2_regulate_IIS_activity_in_the_entire_body_/3079273", "title"=>"GBP1 and GBP2 regulate IIS activity in the entire body.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785220", "https://ndownloader.figshare.com/files/4785247", "https://ndownloader.figshare.com/files/4785265", "https://ndownloader.figshare.com/files/4785277", "https://ndownloader.figshare.com/files/4785292", "https://ndownloader.figshare.com/files/4785322", "https://ndownloader.figshare.com/files/4785343", "https://ndownloader.figshare.com/files/4785388", "https://ndownloader.figshare.com/files/4785418"], "description"=>"<div><p>In <i>Drosophila</i>, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size.</p></div>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3078967, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1002392.s001", "https://dx.doi.org/10.1371/journal.pbio.1002392.s002", "https://dx.doi.org/10.1371/journal.pbio.1002392.s003", "https://dx.doi.org/10.1371/journal.pbio.1002392.s004", "https://dx.doi.org/10.1371/journal.pbio.1002392.s005", "https://dx.doi.org/10.1371/journal.pbio.1002392.s006", "https://dx.doi.org/10.1371/journal.pbio.1002392.s007", "https://dx.doi.org/10.1371/journal.pbio.1002392.s008", "https://dx.doi.org/10.1371/journal.pbio.1002392.s009"], "stats"=>{"downloads"=>15, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Growth_Blocking_Peptides_As_Nutrition_Sensitive_Signals_for_Insulin_Secretion_and_Body_Size_Regulation/3078967", "title"=>"Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785517"], "description"=>"<p><b>(A, B)</b> Changing TOR signaling in the fat body affects final body size in females (A) and males (B). <i>n</i> = 47–72 for A and <i>n</i> = 44–70 for B. Pharate adults (approximately 2–14 h before eclosion) were weighed as a proxy of final adult size. <b>(C)</b> Activating TOR signaling in the fat body does not affect growth rate while repressing TOR signaling reduces growth rate. <i>n</i> = 14–17/time point. <b>(D)</b> Activating TOR signaling in the fat body slightly shortens the duration of the L3. Repressing TOR signaling in the fat body extends the duration of the L3. <i>n</i> = 77–113. Two copies of UAS transgenes were expressed using the <i>C7</i> Gal4 driver in all experiments. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (<i>p</i> < 0.05, ANOVA and pairwise <i>t</i> tests). Growth rate was analyzed by ANCOVA and post hoc comparisons of the slopes. The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079120, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g001", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Changing_TOR_signaling_activity_in_the_fat_body_affects_body_size_/3079120", "title"=>"Changing TOR signaling activity in the fat body affects body size.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785562"], "description"=>"<p><b>(A, B)</b> GBP1, GBP2 double-knockdown in the fat body reduces final body size in females (A) and males (B). <i>n</i> = 35–65 for A and <i>n</i> = 21–56 for B. <b>(C)</b> GBP1, GBP2 double-knockdown in the fat body reduces growth rate. <i>n</i> = 14–17/time point. <b>(D)</b> GBP1, GBP2 double-knockdown extends the duration of the L3. <i>n</i> = 77–115. To compensate the effect of transgenes, we overexpressed two copies of UAS transgenes using the <i>C7</i> Gal4 driver for A–D. <b>(E)</b> <i>gbp1</i>, <i>gbp2 ex67</i> mutation was created using a P-element excision mutagenesis method. The <i>gbp1</i>, <i>gbp2 ex67</i> mutant lacks 1525 bp from the P-element insertion site, which includes the entire <i>gbp1</i> gene and one-third of the second exon of <i>gbp2</i> gene. Open boxes indicate untranslated regions and colored boxes indicate open reading frames. <i>gbp1</i> qPCR and <i>gbp2</i> qPCR indicate the region we amplified for the evaluation of mRNA expression in the <i>gbp1</i>, <i>gbp2 ex67</i> mutant by qPCR in F. <b>(F)</b> The <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows no <i>gbp1</i> and <i>gbp2</i> mRNA expression. We normalized the values using an internal control, <i>RpL3</i>. Then, we standardized the expression level of each gene by fixing the values from w1118 animals to 1. We used five larvae for each sample and five biologically independent samples for each genotype. Each bar indicates the relative mean expression ± standard error of the mean (SEM). <b>(G, H)</b> <i>gbp1</i>, <i>gbp2 ex67</i> mutant animals show reduced body size both in females (G) and males (H). <i>n</i> = 49–69 for G and <i>n</i> = 49–76 for H. <b>(I, J)</b> <i>gbp1</i>, <i>gbp2 ex67</i> mutant animals are smaller than heterozygous animals. Pupae shortly before eclosion (I) and 1-d-old female adults (J) of mutant and heterozygote animals were photographed. Scale bars are 1 mm. <b>(K)</b> <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows reduced growth rate. <i>n</i> = 14–43/time point. <b>(L)</b> <i>gbp1</i>, <i>gbp2 ex67</i> mutant shows extended duration of the L3. <i>n</i> = 84–109. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (<i>p</i> < 0.05, ANOVA and pairwise <i>t</i> tests). Growth rate was analyzed by ANCOVA and post hoc comparisons of the slopes. The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079159, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Reducing_GBP1_and_GBP2_expression_in_the_fat_body_reduces_body_size_due_to_reduced_growth_rate_/3079159", "title"=>"Reducing GBP1 and GBP2 expression in the fat body reduces body size due to reduced growth rate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785610"], "description"=>"<p><b>(A, B)</b> Amino acid intake is sufficient to induce <i>gbp1</i> (A) and <i>gbp2</i> (B) mRNA expression in the fat body of w1118 larvae. Larvae were staged at the onset of the L3, and fed on normal food for 12 h. Then they were starved for 12 h on 1% non-nutritive agar followed by an additional 12 h on one of five nutritionally different media. Columns sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). <b>(C, D)</b> Reducing TOR signaling activity in the fat body decreases <i>gbp1</i> (C) and <i>gbp2</i> (D) mRNA expression in the fat body. Larvae were staged at the onset of the L3, and fed on normal food for 24 h. Numbers indicate p-values (ANOVA and pairwise <i>t</i> tests). We normalized the values using an internal control, <i>RpL3</i>. Then, we standardized the expression level of each gene by fixing the values from non-nutritive agar treated animals to 1 in A and B, and from <i>C7</i>>2xGFP to 1 in C and D. We used the fat bodies from five larvae for each sample and five biologically independent samples for each condition. Each bar indicates the relative mean expression ± SEM. The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079198, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Nutrition_regulates_i_gbp1_i_and_i_gbp2_i_expression_via_TOR_signaling_in_the_fat_body_/3079198", "title"=>"Nutrition regulates <i>gbp1</i> and <i>gbp2</i> expression via TOR signaling in the fat body.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/4785745"], "description"=>"<p><b>(A, B)</b> Overexpressing either GBP1 or GBP2 partially rescues body size reduction in females (A) and males (B) with reduced TOR signaling in their fat bodies. <i>n</i> = 47–64 for A and 59–67 for B. <b>(C)</b> Overexpressing either GBP1 or GBP2 partially increases growth rate in larvae with reduced TOR signaling in the fat body. <i>n</i> = 14-18/time point. <b>(D)</b> Overexpressing either GBP1 or GBP2 partially rescues the duration of the L3 in TOR signaling reduced larvae. <i>n</i> = 108–129. <b>(E, F)</b> Overexpressing either GBP1 or GBP2 reduces ILP2 (E) and ILP5 (F) accumulation in the insulin-producing cells. <b>(G, H)</b> Overexpressing GBP1 or GBP2 reduces the densities of ILP2 (G) and ILP5 (H) signals in the insulin-producing cells. We standardized the densities of ILPs by fixing the values from <i>C7</i>>GFP, TSC1, TSC2 to 1. <i>n</i> = 30–42 for both ILP2 and ILP5. <b>(I)</b> Overexpressing either GBP1 or GBP2 reduces FRE-luciferase activity in the entire body. <i>n</i> = 5. One copy of UAS transgene, UAS TSC1 and UAS TSC2 (three UAS in total) were co-expressed using the <i>C7</i> Gal4 driver for all experiments. For the wild-type control, we overexpressed three copies of UAS GFP using the <i>C7</i> Gal4 driver. Treatments sharing the same letter indicate the groups that are statistically indistinguishable from one another (ANOVA and pairwise <i>t</i> tests, <i>p</i> < 0.05). Growth rate was analyzed by ANCOVA and post hoc comparisons of the slopes. The supplementary file in which the data used to generate each plot can be found is <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002392#pbio.1002392.s001\" target=\"_blank\">S1 Data</a>.</p>", "links"=>[], "tags"=>["Body Size Regulation", "TOR", "body senses intracellular", "Insulin Secretion", "body results", "control body size", "GBP 1", "GBP 2", "growth rate", "body size", "CG 11395", "ILP secretion"], "article_id"=>3079333, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Computational Biology"], "users"=>["Takashi Koyama", "Christen K. Mirth"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002392.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/GBP1_and_GBP2_are_downstream_of_TOR_signaling_/3079333", "title"=>"GBP1 and GBP2 are downstream of TOR signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-29 07:36:38"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}

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