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Articles 1 - 30 of 33

Full-Text Articles in Molecular Biology

Investigation For Novel Anti-Apoptotic Factors In The Neurons Of Drosophila Melanogaster, Haylie Rachel Lam May 2018

Investigation For Novel Anti-Apoptotic Factors In The Neurons Of Drosophila Melanogaster, Haylie Rachel Lam

Chancellor’s Honors Program Projects

No abstract provided.


Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach Jan 2018

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding ...


A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati Sep 2017

A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati

All Dissertations, Theses, and Capstone Projects

With increased understanding of their roles in signal transduction and metabolism, eicosanoids have emerged as important players in human health and disease. Mammalian prostanoids and related lipid mediators perform varied functions in different tissues and organs. Synthesized through the oxygenation of C20 polyunsaturated fatty acids, mammalian eicosanoids are both pro- and anti-inflammatory. The physiological contexts in which eicosanoid family members act at the cellular level are not well understood. In this study, we examined whether the genome of Drosophila melanogaster, a powerful model for innate immunity and inflammation, codes for the enzymes required for eicosanoid biosynthesis. We report the existence ...


A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf May 2017

A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf

Theses and Dissertations

Lipins are a family of proteins that have critical functions in the control of fat storage and energy homeostasis. Biochemically, lipins have two functions. They provide an enzymatic activity (phosphatidate phosphatase or PAP activity) in the glycerol-3 phosphate pathway that leads to the production of storage fats (triacylglycerols). In addition, they play a role in the regulation of genes in the cell nucleus as transcriptional co-regulators. The PAP activity of lipins has been widely studied in a number of organisms. However, the transcriptional co-regulator function is not as well described in the literature. The transcriptional function of lipins depends on ...


Regulation Of The Drosophila Initiator Caspase Dronc Through Ubiquitylation, Hatem E. Kamber Kaya Jan 2017

Regulation Of The Drosophila Initiator Caspase Dronc Through Ubiquitylation, Hatem E. Kamber Kaya

GSBS Dissertations and Theses

Apoptosis is a programmed cell death mechanism that is evolutionary conserved from worms to humans. Apoptosis is mediated by initiator and effector caspases. The initiator caspases carry long pro-domains for their interaction with scaffolding proteins to form a cell-death platform, which is essential for their activation. Activated initiator caspases then cleave effector caspases that execute cell death through cleaving downstream targets. In addition to their apoptotic function, caspases also participate in events where caspase activity is not required for cell killing, but for regulating other functions, so-called non-apoptotic functions of caspases. The Drosophila initiator caspase Dronc, the ortholog of mammalian ...


Functional Significance Of Branch Points In Mirtrons, Britton A. Strickland Dec 2016

Functional Significance Of Branch Points In Mirtrons, Britton A. Strickland

Honors Theses

MicroRNAs are a heterogeneous group of small regulatory RNAs generated by many pathways. Mirtrons (miR) are a class of microRNAs produced by splicing, and some mirtrons contain a 3’ tail located downstream from the self-complementary hairpin. During RNA splicing, a loop-like “lariat” intermediate structure is created when the 5’ end of the RNA is attached to an adenine called the branch point. The goal of this project is to uncover the contribution of branch point location to the processing of tailed mirtrons into functional gene regulators. This project approaches this issue from two directions. First, branch points were identified by ...


Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang Dec 2016

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

UT GSBS Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu Jan 2016

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone ...


A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi Jan 2016

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly ...


Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros Oct 2015

Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros

Victor R. Ambros

The Drosophila let-7-Complex (let-7-C) is a polycistronic locus encoding three ancient microRNAs: let-7, miR-100, and fly lin-4 (miR-125). We find that the let-7-C locus is principally expressed in the pupal and adult neuromusculature. let-7-C knockout flies appear normal externally but display defects in adult behaviors (e.g., flight, motility, and fertility) as well as clear juvenile features in their neuromusculature. We find that the function of let-7-C to ensure the appropriate remodeling of the abdominal neuromusculature during the larval-to-adult transition is carried out predominantly by let-7 alone. This heterochronic role of let-7 is likely just one of the ways in ...


Investigating Notch Signaling And Sequential Segmentation In The Fairy Shrimp, Thamnocephalus Platyurus, Sara Izzat Khalil Apr 2015

Investigating Notch Signaling And Sequential Segmentation In The Fairy Shrimp, Thamnocephalus Platyurus, Sara Izzat Khalil

Senior Theses and Projects

Segmentation is a key feature of arthropod diversity and evolution. In the standard model for arthropod development, Drosophila melanogaster, segments develop simultaneously by a progressive subdivision of the embryo. By contrast, most arthropods add segments sequentially from a posterior region called the growth zone and in a manner similar to vertebrates.

Recent work, mainly focused on insects, suggests that Notch signaling might play a role in arthropods that segment sequentially. These studies document a potential regulatory similarity between sequentially segmenting arthropods and vertebrates. In vertebrates, somite formation involves a molecular oscillator that functions as a pacemaker, driving periodic expression of ...


Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan Jan 2015

Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan

Wayne State University Dissertations

SIN3, the scaffold protein of a histone modifying complex is conserved from yeast to mammals. Drosophila SIN3 associates with both a histone deactylase RPD3 and a histone demethylase dKDM5/LID. Immunopurification of dKDM5/LID verifies a previously observed interaction with SIN3 and RPD3. Furthermore, deficiency of dKDM5/LID phenocopies deficiency of SIN3 in many cellular and developmental processes. Knockdown of both Sin3A and lid hinder cell proliferation in Drosophila cultured cells and developing flies. Knockdown of these genes also results in a curved wing phenotype implicating a role in wing development. Analysis of underlying gene expression changes upon decreased expression ...


A Protective Role Of Autophagy In A Drosophila Model Of Friedreich's Ataxia (Frda), Luan Wang Jan 2015

A Protective Role Of Autophagy In A Drosophila Model Of Friedreich's Ataxia (Frda), Luan Wang

Wayne State University Dissertations

Friedreich’s ataxia (FRDA) is an inherited autosomal recessive neurodegenerative disease. It affects 1 in every 50,000 people in central Europe and North America. FRDA is caused by deficiency of Frataxin, an essential mitochondrial iron chaperone protein, and the associated oxidative stress damages. Autophagy, a housekeeping process responsible for the bulk degradation and turnover of long half-life proteins and organelles, is featured by the formation of double-membrane vacuoles and lysosomal degradation. Previous researches indicate that Danon’s disease, the inherited neural disorder disease that shares similar symptoms with FRDA, is due to the malfunction of autophagy. Based on this ...


Drosophila Cyclin J And The Somatic Pirna Pathway Cooperate To Regulate Germline Stem Cells, Paul Michael Albosta Jan 2015

Drosophila Cyclin J And The Somatic Pirna Pathway Cooperate To Regulate Germline Stem Cells, Paul Michael Albosta

Wayne State University Dissertations

Cyclin J (CycJ) is a highly conserved cyclin that is uniquely expressed specifically in ovaries in Drosophila. Deletion of the genomic region containing CycJ and adjacent genes resulted in a genetic interaction with neighboring piRNA pathway gene, armitage (armi). Here I assessed oogenesis in CycJ null in the presence or absence of mutations in armi or other piRNA pathway genes. Although CycJ null flies had decreased egg laying and hatching rates, ovaries appeared normal indicating that CycJ is dispensable for oogenesis under normal conditions. Further double mutant analysis of CycJ and neighbor armi, as well as two other piRNA pathway ...


Signaling Functions Of Beta-Arrestin Kurtz In Drosophila Development, Marla Tipping Jun 2014

Signaling Functions Of Beta-Arrestin Kurtz In Drosophila Development, Marla Tipping

Marla Tipping, Ph.D.

The development of an organism is orchestrated by a small number of signaling pathways. In order to achieve tissue specificity, their activities are controlled by multiple regulatory molecules that fine-tune pathway output and increase the specificity of signaling. To better understand how these pathways function it is imperative that we strive to elucidate all signaling components. Affinity purification followed by Mass Spectrometry (AP-MS) has proved itself as a suitable technique in achieving this aim. Analysis of the Notch pathway via this method has identified Drosophila β-arrestin Kurtz (Krz) as a negative modulator of the pathway. I have further studied Krz ...


Sex And Heterochromatin: An Investigation Of Sexual Dimorphism In Drosophila Melanogaster, Manasi S. Apte Jan 2014

Sex And Heterochromatin: An Investigation Of Sexual Dimorphism In Drosophila Melanogaster, Manasi S. Apte

Wayne State University Dissertations

Over 30% of Drosophila genome is assembled into heterochromatin. Heterochromatin is relatively gene poor, transcriptionally less active and remains condensed during interphase. Previous studies established that roX RNA and some of the Male Specific Lethal (MSL) proteins, all components of the dosage compensation complex, are required for full expression of autosomal heterochromatic genes in male flies but not in females. This was surprising since heterochromatin is generally not thought to be sexually dimorphic. The genetic basis for the regulation of sex-specific heterochromatin was completely unknown.

To determine if roX RNAs localize directly at the heterochromatic regions that they regulate, I ...


Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang Jan 2014

Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang

Graduate Theses and Dissertations

In Drosophila, JIL-1 Kinase specifically localizes to euchromatic interband regions of polytene chromosomes and is responsible for histone H3S10 phosphorylation at interphase. Previous genetic interaction assays have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components Su(var)3-7 on position-effect variegation (PEV). In this study, we show that the haplo-enhancer effect of JIL-1 has the ability to counterbalance the haplo-suppressor effect of two other major heterochromatin components, Su(var)3-9 and Su(var)2-5, on position-effect variegation, providing evidence that a finely tuned balance between the levels of JIL-1 and the major heterochromatin components ...


Regulation Of Sleep And Circadian Rhythms By Metabolic Neuropeptides, Renske Erion Jan 2014

Regulation Of Sleep And Circadian Rhythms By Metabolic Neuropeptides, Renske Erion

Publicly Accessible Penn Dissertations

The increasing prevalence of metabolic disease in modern society has accelerated our need to understand factors that may be contributing to its development. Both circadian disruption and sleep deprivation are associated with metabolic dysfunction. Thus, for my dissertation I sought to gain insight into this association by studying the genetic and neural basis of interactions between circadian rhythms, sleep and metabolism. The relative simplicity of fly neuroanatomy and physiology, vast array of available genetic tools, and conservation across many organisms, makes Drosophila melanogaster an ideal model to dissect complex interactions between physiological systems. Through our studies we identified a novel ...


Regulation Of Chromosome Segregation In Drosophila Meiosis, Zhi Hao Guo Jan 2014

Regulation Of Chromosome Segregation In Drosophila Meiosis, Zhi Hao Guo

Electronic Theses and Dissertations

Sister-chromatid cohesion is maintained by Cohesin complex. Separase releases the cohesion through the cleavage of the kleisin subunit of Cohesin complex. Separase is regulated by its inhibitor, Securin/Pim. These processes are well studied in mitosis but little is known for meiosis. I found that Separase is required for the proper separation of homologous chromosomes and sister chromatids in Drosophila meiosis. Its function is inhibited by Securin/Pim during the process. I showed that the common kleisin subunit, Rad21, is not likely to be the meiotic target of Separase and that Rad21 and another common Cohesin component, SMC3/CAP, does ...


Studies On Solo Working Mechanism In The Meiosis Of Drosophila Melanogaster, Qian Ma Aug 2013

Studies On Solo Working Mechanism In The Meiosis Of Drosophila Melanogaster, Qian Ma

Masters Theses

In eukaryotes, sister chromatids are closely aligned due to cohesion, a process essential for chromosome pairing and segregation during both mitosis and meiosis. A conserved cohesin complex in a ring structure is composed of four subunits, including each of these four members or their homologs, SMC1, SMC3, SCC1/RAD21/REC8, and SCC3/SA. Up to now, no REC8 homolog has been identified in the meiosis of Drosophila. SOLO is a meiotic protein required for accurate chromosome segregation, centromere cohesion, and cohesin complex localization in Drosophila meiosis. In addition, SOLO is required for synapsis and recombination in Drosophila female meiosis.

In ...


Studying Aggregate Formation By Amyotrophic Lateral Sclerosis-Associated Mutant Sod1 Protein In Drosophila Model, Michael Mccarthy Aug 2013

Studying Aggregate Formation By Amyotrophic Lateral Sclerosis-Associated Mutant Sod1 Protein In Drosophila Model, Michael Mccarthy

UT GSBS Dissertations and Theses (Open Access)

A common pathological hallmark of most neurodegenerative disorders is the presence of protein aggregates in the brain. Understanding the regulation of aggregate formation is thus important for elucidating disease pathogenic mechanisms and finding effective preventive avenues and cures. Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a selective neurodegenerative disorder predominantly affecting motor neurons. The majority of ALS cases are sporadic, however, mutations in superoxide dismutase 1 (SOD1) are responsible for about 20% of familial ALS (fALS). Mutated SOD1 proteins are prone to misfold and form protein aggregates, thus representing a good candidate for studying aggregate ...


The Drosophila Interactions Database: Integrating The Interactome And Transcriptome, Thilakam Murali Jan 2013

The Drosophila Interactions Database: Integrating The Interactome And Transcriptome, Thilakam Murali

Wayne State University Dissertations

In this thesis I describe the integration of heterogeneous interaction data for Drosophila into DroID, the Drosophilainteractions database, making it a one-stop public resource for interaction data. I have also made it possible to filter the interaction data using gene expression data to generate context-relevant networks making DroID a one-of-a kind resource for biologists. In the two years since the upgraded DroID has been available, several studies have used the heterogeneous interaction data in DroID to advance our understanding of Drosophila biology thus validating the need for such a resource for biologists. In addition to this, I have identified ...


Cysteine Desulfurase And Isd11: A Drosophila Model, Rahul Ravindran Nair Jan 2013

Cysteine Desulfurase And Isd11: A Drosophila Model, Rahul Ravindran Nair

Wayne State University Theses

ABSTRACT

Cysteine desulfurase and Isd11: A Drosophila model

Iron-sulfur clusters are cofactors with evolutionary origins that date back to the pre-biotic world. Ever since life originated, these cofactors have intermingled with proteins to play vital roles in sustaining life. My research focuses on one such protein, the cysteine desulfurase (Nfs) that has the PLP cofactor incorporated in its active site and avails of the catalytic property of PLP to provide sulphur for Iron-sulfur cluster biogenesis and assembly in a cell. Interestingly, in a eukaryotic cell, despite the versatility of PLP, cysteine desulfurase's role as a "sulphur-extractor" is incomplete without ...


Characterizing Cyclin J By Identifying Conserved Protein-Protein Interactions, Phillip Jacob Selman Jan 2013

Characterizing Cyclin J By Identifying Conserved Protein-Protein Interactions, Phillip Jacob Selman

Wayne State University Theses

Cyclins are proteins that bind to Cyclin-dependent kinases, or Cdks, through a conserved domain called the Cyclin Box. Many Cyclins regulate the cell cycle. A few Cyclins impact cellular processes outside of the cell cycle. Also, a few Cyclins have poorly understood functions.

Cyclin J is a member of the Cyclin superfamily of proteins. Cyclin J is conserved among all metazoans, but is presently not well understood. All the research done on Cyclin J has been done in Drosophila.

Its mRNA is present in the early embryo, then disappears, only to reappear in adult females. When probing protein extracts with ...


Characterization Of The Ribosomal Protein L22e Family In Drosophila Melanogaster: Evidence For Functional Diversification Of Duplicated Ribosomal Protein Genes, Michael G. Kearse Jan 2013

Characterization Of The Ribosomal Protein L22e Family In Drosophila Melanogaster: Evidence For Functional Diversification Of Duplicated Ribosomal Protein Genes, Michael G. Kearse

Theses and Dissertations

Gene duplication is a contributing factor to genome evolution in eukaryotes. With an additional copy, selective pressure is relieved, allowing for accumulation of genetic variation and possible development of new or altered functions. Ribosomal protein (Rp) genes are a common class of duplicated genes found throughout eukaryotes. Typically encoding highly similar or identical proteins at separate loci, duplicated Rps were originally thought to be redundant and to relieve the high demand for translation. However, recent reports in yeast have shown phenotypic differences between Rp paralogue knockouts, suggesting functional non-redundancy. Little effort has been devoted toward elucidating the function of Rp ...


Recombinant Production Of Vitronectin And Insights Into Its Structure And Role In Fibrinolysis, Cameron T. Landers May 2011

Recombinant Production Of Vitronectin And Insights Into Its Structure And Role In Fibrinolysis, Cameron T. Landers

Chancellor’s Honors Program Projects

No abstract provided.


Analysis Of The Crmp Gene In Drosophila: Determining The Regulatory Role Of Crmp In Signaling And Behavior, Deanna Hardt Morris Jan 2010

Analysis Of The Crmp Gene In Drosophila: Determining The Regulatory Role Of Crmp In Signaling And Behavior, Deanna Hardt Morris

University of Kentucky Doctoral Dissertations

The mammalian genome encodes five collapsin response mediator protein (CRMP) isoforms. Cell culture studies have shown that the CRMPs mediate growth cone dynamics and neuron polarity through associations with a variety of signal transduction components and cytoskeletal elements. CRMP is also a member of a protein family including the presumably ancestral dihydropyrimidinase (DHP) protein that catalyzes the second step in pyrimidine degradation. In Drosophila, CRMP and DHP proteins are produced by alternatively spliced transcripts of the CRMP gene. The alternative protein forms have a 91% sequence identity, but unique expression patterns. CRMP is found exclusively in neuronal tissues and DHP ...


Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis Dec 2009

Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis

Neal Silverman

In this review, we discuss recent advances in understanding the signaling pathways in mammalian and Drosophila innate immunity, with emphasis on the mechanisms by which NF-kappaB/Rel family proteins are activated.


The Bax/Bak Ortholog In Drosophila, Debcl, Exerts Limited Control Over Programmed Cell Death, Kathleen Galindo, Wan-Jin Lu, Jae Park, John Abrams Jan 2009

The Bax/Bak Ortholog In Drosophila, Debcl, Exerts Limited Control Over Programmed Cell Death, Kathleen Galindo, Wan-Jin Lu, Jae Park, John Abrams

Jae H. Park

Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by causing the release of cytochrome c from the mitochondria, a step necessary for the initiation of the caspase cascade. Worms and flies do not show a requirement for cytochrome c during apoptosis, but both model systems express pro- and anti-apoptotic Bcl-2 family members. Drosophila encodes two Bcl-2 family members, Debcl (pro-apoptotic) and Buffy (anti-apoptotic). To understand the role of Debcl in Drosophila apoptosis, we produced authentic null alleles at this locus. Although gross development and lifespans were unaffected ...