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Table S2. Genes Differentially Expressed Between Human and Chimpanzee Brain We Calculated Differential Expression Using a Mask A

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Table S2. Genes differentially expressed between human and chimpanzee brain We calculated differential expression using a mask accounting only for sequence differences between species (species mask only) or the combination of this species mask and a second mask removing probes with multiple hits in either genome (species and unique mask). This table compares the results from these two different analyses. All genes differentially expressed between human and chimpanzee brain with either mask are listed. To be called differentially expressed, a gene had to be significant with p<0.05 in t-test after Benjamini-Hochberg correction for multiple testing (p), have a fold change (FC) of >1.2, and a difference in unlogged units of expression (UD) of >20. The last columns indicate to which TF family a TF belongs (TF family), if a gene associated with any TF (TA), and if a TF in the brain wTO network (N). nd=not detected, and includes genes with detection p-value >0.05 as well as probesets that included too few probes (<4) after masking for accurate detection. Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N 76P 0.002101 1.276145 220.3311 Yes 0.000264 1.346755 372.3989 Yes no TF Yes No AASS 0.050991 1.2218027.451443 No 0.0334021.35444 54.41867Yes no TF Yes No ABCA8 0.019492 2.26484 541.6135 Yes 0.010835 2.355025 561.8352 Yes no TF Yes No ABCB10 0.006016 1.963964 100.8908 Yes 0.015467 1.874999 123.7652 Yes no TF Yes No ABCF2 0.000319 2.051627 373.7187 Yes 0.001279 1.547559 204.7208 Yes no TF Yes No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N ABHD6 0.011121 1.409179 276.5826 Yes 0.014998 1.344751 210.2857 Yes no TF Yes No ABI3BP 0.00081 2.245241193.6929 Yes nd nd nd No no TF No No ACAD11 0.048372 1.246835 83.37943 Yes 0.046995 1.242362 85.30523 Yes no TF Yes No ACAD8 0.000503 2.440463 126.973 Yes 0.000796 2.130244 141.8243 Yes no TF Yes No ACADM 0.001751 4.6452 782.0687 Yes 0.000435 1.820035 418.5473 Yes no TF Yes No ACN9 nd nd nd No 0.0026581.589313 60.63251Yes no TF Yes No ACOT6 0.001308 1.994079 67.9982 Yes 0.001219 2.007423 68.1632 Yes no TF No No ACOX1 0.063043 1.48674 131.2432 No 0.040309 1.504971 153.9699 Yes no TF Yes No ACOX3 0.065208 1.263293 87.54937 No 0.011075 1.852469 155.3061 Yes no TF No No ACP6 nd nd nd No 0.0007841.599693 195.6229Yes no TF Yes No ACTR6 0.00597 1.280672 90.78578 Yes 0.009122 1.239558 80.01446 Yes no TF Yes No ACVR1C 0.042562 1.437522 173.0288 Yes 0.065808 1.399339 137.1889 No no TF No No ACY1 0.031354 1.2142 97.37801 Yes 0.013163 1.206433 94.08058 Yes no TF Yes No ACYP2 0.001014 1.51936 1160.892 Yes 0.00116 1.563708 1294.391 Yes no TF Yes No ADAMTS13 nd nd nd No 0.0055081.353308 116.0457Yes no TF Yes No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N ADARB1 0.014177 1.287386 99.67365 Yes 0.013163 1.289545 103.6576 Yes no TF Yes No ADARB2 0.033092 1.701972 150.8255 Yes 0.039596 1.683925 118.1544 Yes no TF No No ADAT1 0.002213 1.594694 143.0566 Yes 0.002032 1.592908 145.5218 Yes no TF Yes No ADCY5 0.006562 1.338739 212.779 Yes 0.006501 1.33322 209.3532 Yes no TF Yes No ADCY9 0.022026 1.258689 163.1216 Yes 0.024781 1.297741 213.1414 Yes no TF Yes No ADSSL1 0.006562 2.08415 219.7116 Yes 0.006958 2.025943 211.5599 Yes no TF Yes No AGGF1 0.009323 1.239582 82.25923 Yes 0.04399 1.155299 55.67235 No no TF No No AGTPBP1 0.024446 1.292796 176.2424 Yes 0.024333 1.288847 170.4615 Yes no TF Yes No AGTRL1 0.021636 1.297244 66.35472 Yes 0.02216 1.292676 64.86617 Yes no TF No No AHCY 0.036105 1.383558 204.4338 Yes 0.029619 1.338778 317.6586 Yes no TF Yes No AHDC1 nd nd nd No 0.0375351.289134 55.92248Yes no TF No No AHR 0.027738 1.368265 25.48613 Yes 0.02673 1.3651 25.95165 Yes bHLH Yes Yes AIG1 0.018962 1.282828 45.78286 Yes 0.018332 1.280015 44.97098 Yes no TF Yes No AIP 0.005009 1.276919 147.7823 Yes 0.00174 1.277941 210.1154 Yes no TF Yes No AKAP1 0.010825 1.469467 317.8906 Yes 0.039731 1.229086 158.4778 Yes no TF Yes No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N AKAP12 0.003161 1.600293 279.3965 Yes 0.002693 1.815279 366.2747 Yes no TF Yes No AKAP13 0.005903 1.211375 38.68919 Yes 0.015702 1.157842 35.65921 No no TF No No AKAP2 /// PALM2 0.001178 2.040926 467.5931 Yes 0.014357 1.473919 256.6468 Yes no TF Yes No /// AKAP2 AKAP7 0.048564 1.09881322.37779 No 0.0213741.20076 37.77528Yes no TF Yes No AKR1C2 0.001794 1.369747 25.37059 Yes 0.010986 1.480714 23.87766 Yes no TF Yes No ALDH1B1 0.002356 1.471902 92.88785 Yes 0.000389 1.852536 266.7046 Yes no TF Yes No ALDH4A1 0.051087 2.058441 390.8274 No 0.04867 2.045467 344.5559 Yes no TF No No ALKBH6 0.020543 1.375679 265.9807 Yes 0.049461 1.303788 109.6423 Yes no TF Yes No ALKBH7 0.03827 1.329279 172.7658 Yes 0.025259 1.354803 184.4019 Yes no TF Yes No ALKBH8 0.025055 1.394347 49.5901 Yes 0.023376 1.401132 49.68115 Yes no TF Yes No AMD1 0.004908 1.669955 816.0521 Yes 0.000717 1.597406 775.324 Yes no TF Yes No AMOTL1 0.005291 1.294998 121.3228 Yes 0.004976 1.297056 121.2908 Yes no TF Yes No AMOTL2 0.005837 1.783513 672.4175 Yes 0.003451 1.510262 610.6037 Yes no TF Yes No AMY1A /// 0.046693 1.86855 255.3497Yes nd nd nd No no TF No No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N AMY1B /// AMY1C /// AMY2A /// AMY2B /// LOC647537 /// LOC648759 ANAPC1 0.017764 1.72883553.79848 Yes nd nd nd No no TF No No ANAPC11 /// 0.037763 1.231691713.1763 Yes nd nd nd No no TF No No LOC653419 /// LOC653531 ANAPC13 0.020647 1.234042 636.8533 Yes 0.011085 1.183266 615.4968 No no TF No No ANK2 0.018327 1.28971 133.3404 Yes 0.019568 1.280752 129.8948 Yes no TF Yes No ANKH 0.016163 1.238565 144.7499 Yes 0.028116 1.269343 151.2025 Yes no TF Yes No ANKRD15 0.010451 1.293133 153.1121 Yes 0.739046 1.020918 9.642736 No no TF No No ANKRD20A1 /// 0.013469 1.77481 1335.339Yes nd nd nd No no TF No No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N C21orf81 /// LOC392331 /// ANKRD20A3 /// ANKRD20A2 ANKRD32 0.033605 1.456035 61.77272 Yes 0.029181 1.441938 57.55023 Yes no TF Yes No ANKRD35 0.004895 1.586946 120.8225 Yes 0.004826 1.576776 121.4046 Yes no TF Yes No ANKRD42 0.000772 2.194898 60.25109 Yes 0.000898 2.189725 60.09822 Yes no TF Yes No ANKRD50 0.023379 1.52049 132.133 Yes 0.023732 1.395421 82.56258 Yes no TF Yes No ANTXR2 0.031629 1.411592 30.85628 Yes 0.022472 1.33592 46.9253 Yes no TF Yes No ANXA11 0.036313 1.279827 288.8962 Yes 0.025686 1.277403 250.7413 Yes no TF Yes No ANXA7 0.031364 1.362032 902.4822 Yes 0.021409 1.41824 730.4276 Yes no TF Yes No AP1M1 0.045333 1.234961 304.7819 Yes 0.058145 1.240652 294.3856 No no TF No No AP1S1 0.023817 1.577823 400.4627 Yes 0.031709 1.435423 193.7643 Yes no TF Yes No AP3S2 0.003099 1.31145 247.1272 Yes 0.003084 1.305691 243.303 Yes no TF Yes No APCS 0.008883 1.204574 52.31179 Yes 0.008709 1.2097 54.32158 Yes no TF Yes No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N APITD1 0.004078 1.841947 97.87374 Yes 0.005508 1.637385 83.79424 Yes no TF Yes No APLP1 0.006196 1.493092 2237.52 Yes 0.007525 1.424696 3595.735 Yes no TF No No APOD 0.004526 1.764687 2818.839 Yes 0.003998 1.768991 2799.754 Yes no TF Yes No APPBP2 0.034098 1.23735 147.4711 Yes 0.036697 1.192816 126.9796 No no TF No No APRT 0.014797 1.383857 222.4486 Yes 0.087568 1.152862 74.90937 No no TF No No AQP1 0.027132 3.100591 664.7193 Yes 0.028293 2.169786 361.2957 Yes no TF Yes No ARF3 0.021892 1.215237 359.9621 Yes 0.054313 1.185262 603.3409 No no TF No No ARHGAP12 0.045773 1.301442 93.99867 Yes 0.100217 1.258422 116.8369 No no TF No No ARHGEF10 0.040534 1.206634 50.55077 Yes 0.221771 1.187891 133.8804 No no TF No No ARL2 0.005963 1.347512 564.3724 Yes 0.005557 1.344626 554.3345 Yes no TF Yes No ARL5A 0.000864 2.095443 415.06 Yes 0.001833 1.715958 312.3087 Yes no TF Yes No ARL6 0.029428 1.458876 106.8218 Yes 0.036544 1.429491 104.1956 Yes no TF Yes No ARL6IP5 0.042562 1.356999 1390.934 Yes 0.038176 1.43259 1107.343 Yes no TF Yes No ARMC9 0.0118 1.403603 119.8374 Yes 0.007222 1.502012 140.5792 Yes no TF No No ARMCX2 0.049976 1.262264 471.8362 Yes 0.11134 1.193735 431.7144 No no TF No No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N ARMET 0.048056 1.288284 310.6634 Yes 0.034978 1.268564 283.0993 Yes no TF Yes No ARS2 0.046272 1.224089 28.99726 Yes 0.972102 1.004144 3.72925 No no TF No No ART3 nd nd nd No 0.0157311.43257 245.1729Yes no TF No No AS3MT 0.035847 1.305624 58.79103 Yes 0.036545 1.300938 57.07597 Yes no TF Yes No ASB13 0.038068 1.345092455.4278 Yes nd nd nd No no TF No No ASB2 0.002354 1.574176 65.57596 Yes 0.002017 1.595786 65.67069 Yes no TF No No ASB3 0.001132 1.556376 562.4019 Yes 0.001095 1.551505 552.1146 Yes no TF Yes No ASCC3L1 0.005366 1.257487 153.489 Yes 0.001462 1.30849 182.0356 Yes no TF Yes No ASCIZ 0.110706 1.226058 261.402 No 0.002184 1.692359 379.2927 Yes no TF Yes No ASPHD1 0.012707 1.254682 358.2324 Yes 0.014647 1.384016 948.1688 Yes no TF No No ASRGL1 0.011785 1.546096 607.908 Yes 0.018609 1.427511 543.273 Yes no TF No No ASS1 0.078115 1.390554 415.2339 No 0.008578 2.010964 619.1624 Yes no TF Yes No ATE1 0.015042 1.114187 19.82747 No 0.01115 1.27694 45.84607 Yes no TF Yes No ATF7IP2 0.027681 1.308615 111.8213 Yes 0.006617 1.328992 138.5746 Yes no TF Yes No ATG12 0.01721 1.533106661.1271 Yes 0.1328831.192347 128.6803No no TF No No Species mask only Species and unique mask Gene p FC UD C p FC UD C TF family TA N ATP13A3 0.224545 1.071806 18.5667 No 0.028098 1.200935 50.17118 Yes no TF Yes No ATP1B3
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    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
  • The Ubiquitination Enzymes of Leishmania Mexicana

    The Ubiquitination Enzymes of Leishmania Mexicana

    The ubiquitination enzymes of Leishmania mexicana Rebecca Jayne Burge Doctor of Philosophy University of York Biology October 2020 Abstract Post-translational modifications such as ubiquitination are important for orchestrating the cellular transformations that occur as the Leishmania parasite differentiates between its main morphological forms, the promastigote and amastigote. Although 20 deubiquitinating enzymes (DUBs) have been partially characterised in Leishmania mexicana, little is known about the role of E1 ubiquitin-activating (E1), E2 ubiquitin- conjugating (E2) and E3 ubiquitin ligase (E3) enzymes in this parasite. Using bioinformatic methods, 2 E1, 13 E2 and 79 E3 genes were identified in the L. mexicana genome. Subsequently, bar-seq analysis of 23 E1, E2 and HECT/RBR E3 null mutants generated in promastigotes using CRISPR-Cas9 revealed that the E2s UBC1/CDC34, UBC2 and UEV1 and the HECT E3 ligase HECT2 are required for successful promastigote to amastigote differentiation and UBA1b, UBC9, UBC14, HECT7 and HECT11 are required for normal proliferation during mouse infection. Null mutants could not be generated for the E1 UBA1a or the E2s UBC3, UBC7, UBC12 and UBC13, suggesting these genes are essential in promastigotes. X-ray crystal structure analysis of UBC2 and UEV1, orthologues of human UBE2N and UBE2V1/UBE2V2 respectively, revealed a heterodimer with a highly conserved structure and interface. Furthermore, recombinant L. mexicana UBA1a was found to load ubiquitin onto UBC2, allowing UBC2- UEV1 to form K63-linked di-ubiquitin chains in vitro. UBC2 was also shown to cooperate with human E3s RNF8 and BIRC2 in vitro to form non-K63-linked polyubiquitin chains, but association of UBC2 with UEV1 inhibits this ability.
  • Emerging Roles of ARHGAP33 in Intracellular Trafficking of Trkb And

    Emerging Roles of ARHGAP33 in Intracellular Trafficking of Trkb And

    ARTICLE Received 21 Oct 2015 | Accepted 4 Jan 2016 | Published 3 Feb 2016 DOI: 10.1038/ncomms10594 OPEN Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders Takanobu Nakazawa1,2,3, Ryota Hashimoto4,5, Kazuto Sakoori1, Yuki Sugaya1, Asami Tanimura1, Yuki Hashimotodani1, Kazutaka Ohi4, Hidenaga Yamamori4,6, Yuka Yasuda4, Satomi Umeda-Yano6, Yuji Kiyama7, Kohtarou Konno8, Takeshi Inoue2, Kazumasa Yokoyama2, Takafumi Inoue9, Shusuke Numata10, Tohru Ohnuma11, Nakao Iwata12, Norio Ozaki13, Hitoshi Hashimoto3,5,14, Masahiko Watanabe8, Toshiya Manabe7, Tadashi Yamamoto2,15, Masatoshi Takeda4,5 & Masanobu Kano1 Intracellular trafficking of receptor proteins is essential for neurons to detect various extra- cellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain pheno- types and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders. 1 Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
  • Gene Standard Deviation MTOR 0.12553731 PRPF38A

    Gene Standard Deviation MTOR 0.12553731 PRPF38A

    BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Gut Gene Standard Deviation MTOR 0.12553731 PRPF38A 0.141472605 EIF2B4 0.154700091 DDX50 0.156333027 SMC3 0.161420017 NFAT5 0.166316903 MAP2K1 0.166585267 KDM1A 0.16904912 RPS6KB1 0.170330192 FCF1 0.170391706 MAP3K7 0.170660513 EIF4E2 0.171572093 TCEB1 0.175363093 CNOT10 0.178975095 SMAD1 0.179164705 NAA15 0.179904998 SETD2 0.180182498 HDAC3 0.183971158 AMMECR1L 0.184195031 CHD4 0.186678211 SF3A3 0.186697697 CNOT4 0.189434633 MTMR14 0.189734199 SMAD4 0.192451524 TLK2 0.192702667 DLG1 0.19336621 COG7 0.193422331 SP1 0.194364189 PPP3R1 0.196430217 ERBB2IP 0.201473001 RAF1 0.206887192 CUL1 0.207514271 VEZF1 0.207579584 SMAD3 0.208159809 TFDP1 0.208834504 VAV2 0.210269344 ADAM17 0.210687138 SMURF2 0.211437666 MRPS5 0.212428684 TMUB2 0.212560675 SRPK2 0.216217428 MAP2K4 0.216345366 VHL 0.219735582 SMURF1 0.221242495 PLCG1 0.221688351 EP300 0.221792349 Sundar R, et al. Gut 2020;0:1–10. doi: 10.1136/gutjnl-2020-320805 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Gut MGAT5 0.222050228 CDC42 0.2230598 DICER1 0.225358787 RBX1 0.228272533 ZFYVE16 0.22831803 PTEN 0.228595789 PDCD10 0.228799406 NF2 0.23091035 TP53 0.232683696 RB1 0.232729172 TCF20 0.2346075 PPP2CB 0.235117302 AGK 0.235416298