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1. Immune Suppressive Extracellular Vesicle Proteins of Leptopilina heterotoma Are Encoded in the Wasp Genome.

Author

Wey B, Heavner ME, Wittmeyer KT, Briese T, Hopper KR, and Govind S

Subjects
Animals, Drosophila immunology, Drosophila parasitology, Extracellular Vesicles metabolism, Female, Insect Proteins metabolism, Male, Proteome genetics, Proteome metabolism, Transcriptome, Wasp Venoms metabolism, Wasps pathogenicity, Extracellular Vesicles genetics, Insect Proteins genetics, Wasp Venoms genetics, Wasps genetics
Abstract

Leptopilina heterotoma are obligate parasitoid wasps that develop in the body of their Drosophila hosts. During oviposition, female wasps introduce venom into the larval hosts' body cavity. The venom contains discrete, 300 nm-wide, mixed-strategy extracellular vesicles (MSEVs), until recently referred to as virus-like particles. While the crucial immune suppressive functions of L. heterotoma MSEVs have remained undisputed, their biotic nature and origin still remain controversial. In recent proteomics analyses of L. heterotoma MSEVs, we identified 161 proteins in three classes: conserved eukaryotic proteins, infection and immunity related proteins, and proteins without clear annotation. Here we report 246 additional proteins from the L. heterotoma MSEV proteome. An enrichment analysis of the entire proteome supports vesicular nature of these structures. Sequences for more than 90% of these proteins are present in the whole-body transcriptome. Sequencing and de novo assembly of the 460 Mb-sized L. heterotoma genome revealed 90% of MSEV proteins have coding regions within the genomic scaffolds. Altogether, these results explain the stable association of MSEVs with their wasps, and like other wasp structures, their vertical inheritance. While our results do not rule out a viral origin of MSEVs, they suggest that a similar strategy for co-opting cellular machinery for immune suppression may be shared by other wasps to gain advantage over their hosts. These results are relevant to our understanding of the evolution of figitid and related wasp species., (Copyright © 2020 Wey et al.)

Published
2020
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3. Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

Author

Leung W, Shaffer CD, Reed LK, Smith ST, Barshop W, Dirkes W, Dothager M, Lee P, Wong J, Xiong D, Yuan H, Bedard JE, Machone JF, Patterson SD, Price AL, Turner BA, Robic S, Luippold EK, McCartha SR, Walji TA, Walker CA, Saville K, Abrams MK, Armstrong AR, Armstrong W, Bailey RJ, Barberi CR, Beck LR, Blaker AL, Blunden CE, Brand JP, Brock EJ, Brooks DW, Brown M, Butzler SC, Clark EM, Clark NB, Collins AA, Cotteleer RJ, Cullimore PR, Dawson SG, Docking CT, Dorsett SL, Dougherty GA, Downey KA, Drake AP, Earl EK, Floyd TG, Forsyth JD, Foust JD, Franchi SL, Geary JF, Hanson CK, Harding TS, Harris CB, Heckman JM, Holderness HL, Howey NA, Jacobs DA, Jewell ES, Kaisler M, Karaska EA, Kehoe JL, Koaches HC, Koehler J, Koenig D, Kujawski AJ, Kus JE, Lammers JA, Leads RR, Leatherman EC, Lippert RN, Messenger GS, Morrow AT, Newcomb V, Plasman HJ, Potocny SJ, Powers MK, Reem RM, Rennhack JP, Reynolds KR, Reynolds LA, Rhee DK, Rivard AB, Ronk AJ, Rooney MB, Rubin LS, Salbert LR, Saluja RK, Schauder T, Schneiter AR, Schulz RW, Smith KE, Spencer S, Swanson BR, Tache MA, Tewilliager AA, Tilot AK, VanEck E, Villerot MM, Vylonis MB, Watson DT, Wurzler JA, Wysocki LM, Yalamanchili M, Zaborowicz MA, Emerson JA, Ortiz C, Deuschle FJ, DiLorenzo LA, Goeller KL, Macchi CR, Muller SE, Pasierb BD, Sable JE, Tucci JM, Tynon M, Dunbar DA, Beken LH, Conturso AC, Danner BL, DeMichele GA, Gonzales JA, Hammond MS, Kelley CV, Kelly EA, Kulich D, Mageeney CM, McCabe NL, Newman AM, Spaeder LA, Tumminello RA, Revie D, Benson JM, Cristostomo MC, DaSilva PA, Harker KS, Jarrell JN, Jimenez LA, Katz BM, Kennedy WR, Kolibas KS, LeBlanc MT, Nguyen TT, Nicolas DS, Patao MD, Patao SM, Rupley BJ, Sessions BJ, Weaver JA, Goodman AL, Alvendia EL, Baldassari SM, Brown AS, Chase IO, Chen M, Chiang S, Cromwell AB, Custer AF, DiTommaso TM, El-Adaimi J, Goscinski NC, Grove RA, Gutierrez N, Harnoto RS, Hedeen H, Hong EL, Hopkins BL, Huerta VF, Khoshabian C, LaForge KM, Lee CT, Lewis BM, Lydon AM, Maniaci BJ, Mitchell RD, Morlock EV, Morris WM, Naik P, Olson NC, Osterloh JM, Perez MA, Presley JD, Randazzo MJ, Regan MK, Rossi FG, Smith MA, Soliterman EA, Sparks CJ, Tran DL, Wan T, Welker AA, Wong JN, Sreenivasan A, Youngblom J, Adams A, Alldredge J, Bryant A, Carranza D, Cifelli A, Coulson K, Debow C, Delacruz N, Emerson C, Farrar C, Foret D, Garibay E, Gooch J, Heslop M, Kaur S, Khan A, Kim V, Lamb T, Lindbeck P, Lucas G, Macias E, Martiniuc D, Mayorga L, Medina J, Membreno N, Messiah S, Neufeld L, Nguyen SF, Nichols Z, Odisho G, Peterson D, Rodela L, Rodriguez P, Rodriguez V, Ruiz J, Sherrill W, Silva V, Sparks J, Statton G, Townsend A, Valdez I, Waters M, Westphal K, Winkler S, Zumkehr J, DeJong RJ, Hoogewerf AJ, Ackerman CM, Armistead IO, Baatenburg L, Borr MJ, Brouwer LK, Burkhart BJ, Bushhouse KT, Cesko L, Choi TY, Cohen H, Damsteegt AM, Darusz JM, Dauphin CM, Davis YP, Diekema EJ, Drewry M, Eisen ME, Faber HM, Faber KJ, Feenstra E, Felzer-Kim IT, Hammond BL, Hendriksma J, Herrold MR, Hilbrands JA, Howell EJ, Jelgerhuis SA, Jelsema TR, Johnson BK, Jones KK, Kim A, Kooienga RD, Menyes EE, Nollet EA, Plescher BE, Rios L, Rose JL, Schepers AJ, Scott G, Smith JR, Sterling AM, Tenney JC, Uitvlugt C, VanDyken RE, VanderVennen M, Vue S, Kokan NP, Agbley K, Boham SK, Broomfield D, Chapman K, Dobbe A, Dobbe I, Harrington W, Ibrahem M, Kennedy A, Koplinsky CA, Kubricky C, Ladzekpo D, Pattison C, Ramirez RE Jr, Wande L, Woehlke S, Wawersik M, Kiernan E, Thompson JS, Banker R, Bartling JR, Bhatiya CI, Boudoures AL, Christiansen L, Fosselman DS, French KM, Gill IS, Havill JT, Johnson JL, Keny LJ, Kerber JM, Klett BM, Kufel CN, May FJ, Mecoli JP, Merry CR, Meyer LR, Miller EG, Mullen GJ, Palozola KC, Pfeil JJ, Thomas JG, Verbofsky EM, Spana EP, Agarwalla A, Chapman J, Chlebina B, Chong I, Falk IN, Fitzgibbons JD, Friedman H, Ighile O, Kim AJ, Knouse KA, Kung F, Mammo D, Ng CL, Nikam VS, Norton D, Pham P, Polk JW, Prasad S, Rankin H, Ratliff CD, Scala V, Schwartz NU, Shuen JA, Xu A, Xu TQ, Zhang Y, Rosenwald AG, Burg MG, Adams SJ, Baker M, Botsford B, Brinkley B, Brown C, Emiah S, Enoch E, Gier C, Greenwell A, Hoogenboom L, Matthews JE, McDonald M, Mercer A, Monsma N, Ostby K, Ramic A, Shallman D, Simon M, Spencer E, Tomkins T, Wendland P, Wylie A, Wolyniak MJ, Robertson GM, Smith SI, DiAngelo JR, Sassu ED, Bhalla SC, Sharif KA, Choeying T, Macias JS, Sanusi F, Torchon K, Bednarski AE, Alvarez CJ, Davis KC, Dunham CA, Grantham AJ, Hare AN, Schottler J, Scott ZW, Kuleck GA, Yu NS, Kaehler MM, Jipp J, Overvoorde PJ, Shoop E, Cyrankowski O, Hoover B, Kusner M, Lin D, Martinov T, Misch J, Salzman G, Schiedermayer H, Snavely M, Zarrasola S, Parrish S, Baker A, Beckett A, Belella C, Bryant J, Conrad T, Fearnow A, Gomez C, Herbstsomer RA, Hirsch S, Johnson C, Jones M, Kabaso R, Lemmon E, Vieira CM, McFarland D, McLaughlin C, Morgan A, Musokotwane S, Neutzling W, Nietmann J, Paluskievicz C, Penn J, Peoples E, Pozmanter C, Reed E, Rigby N, Schmidt L, Shelton M, Shuford R, Tirasawasdichai T, Undem B, Urick D, Vondy K, Yarrington B, Eckdahl TT, Poet JL, Allen AB, Anderson JE, Barnett JM, Baumgardner JS, Brown AD, Carney JE, Chavez RA, Christgen SL, Christie JS, Clary AN, Conn MA, Cooper KM, Crowley MJ, Crowley ST, Doty JS, Dow BA, Edwards CR, Elder DD, Fanning JP, Janssen BM, Lambright AK, Lane CE, Limle AB, Mazur T, McCracken MR, McDonough AM, Melton AD, Minnick PJ, Musick AE, Newhart WH, Noynaert JW, Ogden BJ, Sandusky MW, Schmuecker SM, Shipman AL, Smith AL, Thomsen KM, Unzicker MR, Vernon WB, Winn WW, Woyski DS, Zhu X, Du C, Ament C, Aso S, Bisogno LS, Caronna J, Fefelova N, Lopez L, Malkowitz L, Marra J, Menillo D, Obiorah I, Onsarigo EN, Primus S, Soos M, Tare A, Zidan A, Jones CJ, Aronhalt T, Bellush JM, Burke C, DeFazio S, Does BR, Johnson TD, Keysock N, Knudsen NH, Messler J, Myirski K, Rekai JL, Rempe RM, Salgado MS, Stagaard E, Starcher JR, Waggoner AW, Yemelyanova AK, Hark AT, Bertolet A, Kuschner CE, Parry K, Quach M, Shantzer L, Shaw ME, Smith MA, Glenn O, Mason P, Williams C, Key SC, Henry TC, Johnson AG, White JX, Haberman A, Asinof S, Drumm K, Freeburg T, Safa N, Schultz D, Shevin Y, Svoronos P, Vuong T, Wellinghoff J, Hoopes LL, Chau KM, Ward A, Regisford EG, Augustine L, Davis-Reyes B, Echendu V, Hales J, Ibarra S, Johnson L, Ovu S, Braverman JM, Bahr TJ, Caesar NM, Campana C, Cassidy DW, Cognetti PA, English JD, Fadus MC, Fick CN, Freda PJ, Hennessy BM, Hockenberger K, Jones JK, King JE, Knob CR, Kraftmann KJ, Li L, Lupey LN, Minniti CJ, Minton TF, Moran JV, Mudumbi K, Nordman EC, Puetz WJ, Robinson LM, Rose TJ, Sweeney EP, Timko AS, Paetkau DW, Eisler HL, Aldrup ME, Bodenberg JM, Cole MG, Deranek KM, DeShetler M, Dowd RM, Eckardt AK, Ehret SC, Fese J, Garrett AD, Kammrath A, Kappes ML, Light MR, Meier AC, O'Rouke A, Perella M, Ramsey K, Ramthun JR, Reilly MT, Robinett D, Rossi NL, Schueler MG, Shoemaker E, Starkey KM, Vetor A, Vrable A, Chandrasekaran V, Beck C, Hatfield KR, Herrick DA, Khoury CB, Lea C, Louie CA, Lowell SM, Reynolds TJ, Schibler J, Scoma AH, Smith-Gee MT, Tuberty S, Smith CD, Lopilato JE, Hauke J, Roecklein-Canfield JA, Corrielus M, Gilman H, Intriago S, Maffa A, Rauf SA, Thistle K, Trieu M, Winters J, Yang B, Hauser CR, Abusheikh T, Ashrawi Y, Benitez P, Boudreaux LR, Bourland M, Chavez M, Cruz S, Elliott G, Farek JR, Flohr S, Flores AH, Friedrichs C, Fusco Z, Goodwin Z, Helmreich E, Kiley J, Knepper JM, Langner C, Martinez M, Mendoza C, Naik M, Ochoa A, Ragland N, Raimey E, Rathore S, Reza E, Sadovsky G, Seydoux MI, Smith JE, Unruh AK, Velasquez V, Wolski MW, Gosser Y, Govind S, Clarke-Medley N, Guadron L, Lau D, Lu A, Mazzeo C, Meghdari M, Ng S, Pamnani B, Plante O, Shum YK, Song R, Johnson DE, Abdelnabi M, Archambault A, Chamma N, Gaur S, Hammett D, Kandahari A, Khayrullina G, Kumar S, Lawrence S, Madden N, Mandelbaum M, Milnthorp H, Mohini S, Patel R, Peacock SJ, Perling E, Quintana A, Rahimi M, Ramirez K, Singhal R, Weeks C, Wong T, Gillis AT, Moore ZD, Savell CD, Watson R, Mel SF, Anilkumar AA, Bilinski P, Castillo R, Closser M, Cruz NM, Dai T, Garbagnati GF, Horton LS, Kim D, Lau JH, Liu JZ, Mach SD, Phan TA, Ren Y, Stapleton KE, Strelitz JM, Sunjed R, Stamm J, Anderson MC, Bonifield BG, Coomes D, Dillman A, Durchholz EJ, Fafara-Thompson AE, Gross MJ, Gygi AM, Jackson LE, Johnson A, Kocsisova Z, Manghelli JL, McNeil K, Murillo M, Naylor KL, Neely J, Ogawa EE, Rich A, Rogers A, Spencer JD, Stemler KM, Throm AA, Van Camp M, Weihbrecht K, Wiles TA, Williams MA, Williams M, Zoll K, Bailey C, Zhou L, Balthaser DM, Bashiri A, Bower ME, Florian KA, Ghavam N, Greiner-Sosanko ES, Karim H, Mullen VW, Pelchen CE, Yenerall PM, Zhang J, Rubin MR, Arias-Mejias SM, Bermudez-Capo AG, Bernal-Vega GV, Colon-Vazquez M, Flores-Vazquez A, Gines-Rosario M, Llavona-Cartagena IG, Martinez-Rodriguez JO, Ortiz-Fuentes L, Perez-Colomba EO, Perez-Otero J, Rivera E, Rodriguez-Giron LJ, Santiago-Sanabria AJ, Senquiz-Gonzalez AM, delValle FR, Vargas-Franco D, Velázquez-Soto KI, Zambrana-Burgos JD, Martinez-Cruzado JC, Asencio-Zayas L, Babilonia-Figueroa K, Beauchamp-Pérez FD, Belén-Rodríguez J, Bracero-Quiñones L, Burgos-Bula AP, Collado-Méndez XA, Colón-Cruz LR, Correa-Muller AI, Crooke-Rosado JL, Cruz-García JM, Defendini-Ávila M, Delgado-Peraza FM, Feliciano-Cancela AJ, Gónzalez-Pérez VM, Guiblet W, Heredia-Negrón A, Hernández-Muñiz J, Irizarry-González LN, Laboy-Corales ÁL, Llaurador-Caraballo GA, Marín-Maldonado F, Marrero-Llerena U, Martell-Martínez HA, Martínez-Traverso IM, Medina-Ortega KN, Méndez-Castellanos SG, Menéndez-Serrano KC, Morales-Caraballo CI, Ortiz-DeChoudens S, Ortiz-Ortiz P, Pagán-Torres H, Pérez-Afanador D, Quintana-Torres EM, Ramírez-Aponte EG, Riascos-Cuero C, Rivera-Llovet MS, Rivera-Pagán IT, Rivera-Vicéns RE, Robles-Juarbe F, Rodríguez-Bonilla L, Rodríguez-Echevarría BO, Rodríguez-García PM, Rodríguez-Laboy AE, Rodríguez-Santiago S, Rojas-Vargas ML, Rubio-Marrero EN, Santiago-Colón A, Santiago-Ortiz JL, Santos-Ramos CE, Serrano-González J, Tamayo-Figueroa AM, Tascón-Peñaranda EP, Torres-Castillo JL, Valentín-Feliciano NA, Valentín-Feliciano YM, Vargas-Barreto NM, Vélez-Vázquez M, Vilanova-Vélez LR, Zambrana-Echevarría C, MacKinnon C, Chung HM, Kay C, Pinto A, Kopp OR, Burkhardt J, Harward C, Allen R, Bhat P, Chang JH, Chen Y, Chesley C, Cohn D, DuPuis D, Fasano M, Fazzio N, Gavinski K, Gebreyesus H, Giarla T, Gostelow M, Greenstein R, Gunasinghe H, Hanson C, Hay A, He TJ, Homa K, Howe R, Howenstein J, Huang H, Khatri A, Kim YL, Knowles O, Kong S, Krock R, Kroll M, Kuhn J, Kwong M, Lee B, Lee R, Levine K, Li Y, Liu B, Liu L, Liu M, Lousararian A, Ma J, Mallya A, Manchee C, Marcus J, McDaniel S, Miller ML, Molleston JM, Diez CM, Ng P, Ngai N, Nguyen H, Nylander A, Pollack J, Rastogi S, Reddy H, Regenold N, Sarezky J, Schultz M, Shim J, Skorupa T, Smith K, Spencer SJ, Srikanth P, Stancu G, Stein AP, Strother M, Sudmeier L, Sun M, Sundaram V, Tazudeen N, Tseng A, Tzeng A, Venkat R, Venkataram S, Waldman L, Wang T, Yang H, Yu JY, Zheng Y, Preuss ML, Garcia A, Juergens M, Morris RW, Nagengast AA, Azarewicz J, Carr TJ, Chichearo N, Colgan M, Donegan M, Gardner B, Kolba N, Krumm JL, Lytle S, MacMillian L, Miller M, Montgomery A, Moretti A, Offenbacker B, Polen M, Toth J, Woytanowski J, Kadlec L, Crawford J, Spratt ML, Adams AL, Barnard BK, Cheramie MN, Eime AM, Golden KL, Hawkins AP, Hill JE, Kampmeier JA, Kern CD, Magnuson EE, Miller AR, Morrow CM, Peairs JC, Pickett GL, Popelka SA, Scott AJ, Teepe EJ, TerMeer KA, Watchinski CA, Watson LA, Weber RE, Woodard KA, Barnard DC, Appiah I, Giddens MM, McNeil GP, Adebayo A, Bagaeva K, Chinwong J, Dol C, George E, Haltaufderhyde K, Haye J, Kaur M, Semon M, Serjanov D, Toorie A, Wilson C, Riddle NC, Buhler J, Mardis ER, and Elgin SC

Subjects
Animals, Codon, Computational Biology, DNA Transposable Elements, Drosophila melanogaster genetics, Exons, Gene Rearrangement, Heterochromatin, Introns, Molecular Sequence Annotation, Polytene Chromosomes, Repetitive Sequences, Nucleic Acid, Selection, Genetic, Species Specificity, Drosophila genetics, Drosophila Proteins genetics, Evolution, Molecular, Genome, Genomics
Abstract

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Published
2015
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4. Protection versus pathology in aviremic and high viral load HIV-2 infection-the pivotal role of immune activation and T-cell kinetics.

Author

Hegedus A, Nyamweya S, Zhang Y, Govind S, Aspinall R, Mashanova A, Jansen VA, Whittle H, Jaye A, Flanagan KL, and Macallan DC

Subjects
Adult, Female, Gambia, HIV Long-Term Survivors, Humans, Male, Middle Aged, Young Adult, HIV Infections immunology, HIV Infections virology, HIV-2 immunology, T-Lymphocytes immunology, Viral Load
Abstract

Background: Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status., Methods: We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance., Results: Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls

Published
2014
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5. An unexpected link between notch signaling and ROS in restricting the differentiation of hematopoietic progenitors in Drosophila.

Author

Small C, Ramroop J, Otazo M, Huang LH, Saleque S, and Govind S

Subjects
Animals, Calcium-Binding Proteins genetics, Cell Differentiation, Drosophila melanogaster parasitology, Female, Hematopoiesis, Intercellular Signaling Peptides and Proteins genetics, Jagged-1 Protein, Male, Membrane Proteins genetics, RNA Interference, Serrate-Jagged Proteins, Ubiquitin-Protein Ligases genetics, Wasps, Drosophila Proteins genetics, Drosophila melanogaster genetics, Hematopoietic Stem Cells cytology, Reactive Oxygen Species metabolism, Receptors, Notch genetics, Signal Transduction
Abstract

A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection. We show that Notch activity is moderately high and ubiquitous in all cells of the lymph gland lobes, with crystal cells exhibiting the highest levels. Wasp infection reduces Notch activity, which results in fewer crystal cells and more lamellocytes. Robust lamellocyte differentiation is induced even in N mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. However, unlike its cell-autonomous function in crystal cell development, Notch's inhibitory influence on lamellocyte differentiation is not cell autonomous. High levels of reactive oxygen species in the lymph gland lobes, but not in the niche, accompany N(RNAi)-induced lamellocyte differentiation and lobe dispersal. Our results define a novel dual role for Notch signaling in maintaining competence for basal hematopoiesis: while crystal cell development is encouraged, lamellocytic fate remains repressed. Repression of Notch signaling in fly hematopoiesis is important for host defense against natural parasitic wasp infections. These findings can serve as a model to understand how reactive oxygen species and Notch signals are integrated and interpreted in vivo., (Copyright © 2014 by the Genetics Society of America.)

Published
2014
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6. Impaired myocardial functional reserve in hypertension and diabetes mellitus without coronary artery disease: Searching for the possible link with congestive heart failure in the myocardial Doppler in diabetes (MYDID) study II.

Author

Govind S, Saha S, Brodin LA, Ramesh SS, Arvind SR, and Quintana M

Subjects
Coronary Artery Disease diagnostic imaging, Echocardiography, Doppler, Female, Humans, Male, Middle Aged, Diabetes Mellitus diagnostic imaging, Heart Failure complications, Heart Failure diagnostic imaging, Hypertension complications, Hypertension diagnostic imaging
Abstract

Background: Although the impact of type 2 diabetes mellitus (DM) and hypertension (HTN) on myocardial function has recently been studied using tissue Doppler echocardiography (TDE), the independent role of both conditions, and the influence of other risk factors on myocardial function has not been completely defined, particularly in absence of coronary artery disease (CAD). The aim of this study was to assess the myocardial functional reserve in patients with DM or HTN with apparently normal left ventricular (LV) systolic function., Methods: Standard and dobutamine stress echocardiography using TDE was performed in 128 subjects: 59 had DM, 20 had HTN, 27 had both DM and HTN (HTN + DM), and 22 subjects were controls (C). Subjects with known CAD and depressed LV function were excluded. In addition, standard two-dimensional and Doppler measurements, LV regional peak systolic (PSV), early (E') and late (A') diastolic velocities, strain (S%) and strain rate (SR), were assessed at rest and peak stress., Results: The LV mass did not differ, although relative wall thickness was significantly higher in subjects with HTN + DM and HTN. The PSV did not differ at rest but was lowest in subjects with HTN + DM at peak stress. The E' wave velocity was significantly lower in subjects with HTN + DM both at rest and during peak stress, as were S% and SR., Conclusions: The addition of DM to HTN has a negative effect on LV systolic and diastolic functions. A depressed myocardial functional reserve might be postulated as one of the pathophysiologic mechanisms for the excessive occurrence of congestive heart failure in patients with DM or HTN.

Published
2006
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7. Bilateral femoral capital avascular necrosis in a renal transplant recipient on tacrolimus-based immunosuppression.

Author

Nayagam LS, Rajan SG, Khandelwal N, Sen R, Kohli HS, Sud K, Gupta KL, Sakhuja V, and Jha V

Subjects
Adrenal Cortex Hormones administration & dosage, Adrenal Cortex Hormones adverse effects, Adult, Femur Head Necrosis pathology, Humans, Magnetic Resonance Imaging, Male, Risk Factors, Time Factors, Femur Head Necrosis etiology, Immunosuppressive Agents adverse effects, Kidney Transplantation adverse effects, Tacrolimus adverse effects
Published
2005
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8. Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila.

Author

Sorrentino RP, Melk JP, and Govind S

Subjects
Animals, Cell Count, DNA-Binding Proteins metabolism, Drosophila metabolism, Drosophila Proteins metabolism, Hemocytes classification, Host-Parasite Interactions, Hymenoptera physiology, Insect Viruses, Janus Kinases, Larva parasitology, Mutation, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases metabolism, Receptors, Cell Surface metabolism, STAT Transcription Factors, Toll-Like Receptors, Trans-Activators metabolism, Transcription Factors, DNA-Binding Proteins genetics, Drosophila genetics, Drosophila Proteins genetics, Genes, Insect, Hemocytes cytology, Ovum physiology, Receptors, Cell Surface genetics, Trans-Activators genetics
Abstract

Drosophila larvae defend themselves against parasitoid wasps by completely surrounding the egg with layers of specialized hemocytes called lamellocytes. Similar capsules of lamellocytes, called melanotic capsules, are also formed around "self" tissues in larvae carrying gain-of-function mutations in Toll and hopscotch. Constitutive differentiation of lamellocytes in larvae carrying these mutations is accompanied by high concentrations of plasmatocytes, the major hemocyte class in uninfected control larvae. The relative contributions of hemocyte concentration vs. lamellocyte differentiation to wasp egg encapsulation are not known. To address this question, we used Leptopilina boulardi to infect more than a dozen strains of host larvae harboring a wide range of hemocyte densities. We report a significant correlation between hemocyte concentration and encapsulation capacity among wild-type larvae and larvae heterozygous for mutations in the Hopscotch-Stat92E and Toll-Dorsal pathways. Larvae carrying loss-of-function mutations in Hopscotch, Stat92E, or dorsal group genes exhibit significant reduction in encapsulation capacity. Larvae carrying loss-of-function mutations in dorsal group genes (including Toll and tube) have reduced hemocyte concentrations, whereas larvae deficient in Hopscotch-Stat92E signaling do not. Surprisingly, unlike hopscotch mutants, Toll and tube mutants are not compromised in their ability to generate lamellocytes. Our results suggest that circulating hemocyte concentration and lamellocyte differentiation constitute two distinct physiological requirements of wasp egg encapsulation and Toll and Hopscotch proteins serve distinct roles in this process.

Published
2004
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