Life Sciences Commons^™

Role For Sumoylation In Systemic Inflammation And Immune Homeostasis In Drosophila Larvae, Indira Paddibhatla, Mark J. Lee, Marta E. Kalamarz, Roberto Ferrarese, Shubha Govind

Publications and Research

To counter systemic risk of infection by parasitic wasps, Drosophila larvae activate humoral immunity in the fat body and mount a robust cellular response resulting in encapsulation of the wasp egg. Innate immune reactions are tightly regulated and are resolved within hours. To understand the mechanisms underlying activation and resolution of the egg encapsulation response and examine if failure of the latter develops into systemic inflammatory disease, we correlated parasitic wasp-induced changes in the Drosophila larva with systemic chronic conditions in sumoylation-deficient mutants. We have previously reported that loss of either Cactus, the Drosophila (IkB) protein or Ubc9, the SUMO-conjugating …

Identification Of An Archaeal Presenilin-Like Intramembrane Protease, Celia Torres-Arancivia, Carolyn M. Ross, Jose Chavez, Zahra Assur, Georgia Dolios, Filippo Mancia, Iban Ubarretxena-Belandia

Publications and Research

Background: The GXGD-type diaspartyl intramembrane protease, presenilin, constitutes the catalytic core of the c-secretase multi-protein complex responsible for activating critical signaling cascades during development and for the production of b-amyloid peptides (Ab) implicated in Alzheimer’s disease. The only other known GXGD-type diaspartyl intramembrane proteases are the eukaryotic signal peptide peptidases (SPPs). The presence of presenilin-like enzymes outside eukaryots has not been demonstrated. Here we report the existence of presenilin-like GXGD-type diaspartyl intramembrane proteases in archaea.

Methodology and Principal Findings: We have employed in vitro activity assays to show that MCMJR1, a polytopic membrane protein from the archaeon Methanoculleus marisnigri JR1, …

Drug Off-Target Effects Predicted Using Structural Analysis In The Context Of A Metabolic Network Model, Roger L. Chang, Lei Xie, Philip E. Bourne, Bernhard O. Palsson

Publications and Research

Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been …

Identification And Structural Characterization Of Fyve Domain-Containing Proteins Of Arabidopsis Thaliana, Ewa Wywial, Shaneen M. Singh

Publications and Research

Background FYVE domains have emerged as membrane-targeting domains highly specific for phosphatidylinositol 3-phosphate (PtdIns(3)P). They are predominantly found in proteins involved in various trafficking pathways. Although FYVE domains may function as individual modules, dimers or in partnership with other proteins, structurally, all FYVE domains share a fold comprising two small characteristic double-stranded β-sheets, and a C-terminal α-helix, which houses eight conserved Zn2+ ion-binding cysteines. To date, the structural, biochemical, and biophysical mechanisms for subcellular targeting of FYVE domains for proteins from various model organisms have been worked out but plant FYVE domains remain noticeably under-investigated.

Results We carried out an …

Tyrannobdella Rex N. Gen. N. Sp. And The Evolutionary Origins Of Mucosal Leech Infestations, Anna J. Phillips, Renzo Arauco-Brown, Alejandro Oceguera-Figueroa, Gloria P. Gomez, María Beltrán, Yi-Te Lai, Mark E. Siddall

Publications and Research

Background: Leeches have gained a fearsome reputation by feeding externally on blood, often from human hosts. Orificial hirudiniasis is a condition in which a leech enters a body orifice, most often the nasopharyngeal region, but there are many cases of leeches infesting the eyes, urethra, vagina, or rectum. Several leech species particularly in Africa and Asia are well known for their propensity to afflict humans. Because there has not previously been any data suggesting a close relationship for such geographically disparate species, this unnerving tendency to be invasive has been regarded only as a loathsome oddity and not a unifying …

Antidepressant Stimulation Of Cdp-Diacylglycerol Synthesis Does Not Require Monoamine Reuptake Inhibition, Ashiwel S. Undieh, Marwa A. Aboukhatwa

Publications and Research

Background: Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of …

A Multidimensional Strategy To Detect Polypharmacological Targets In The Absence Of Structural And Sequence Homology, Jacob D. Durrant, Rommie E. Amaro, Lei Xie, Michael D. Urbaniak, Michael A. J. Ferguson, Antti Haapalainen, Zhijun Chen, Anne Marie Di Guilmi, Frank Wunder, Philip E. Bourne, J. Andrew Mccammon

Publications and Research

Conventional drug design embraces the ‘‘one gene, one drug, one disease’’ philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional …

Patterns Of Subnet Usage Reveal Distinct Scales Of Regulation In The Transcriptional Regulatory Network Of Escherichia Coli, Carsten Marr, Fabian J. Theis, Larry S. Liebovitch, Marc-Thorsten Hutt

Publications and Research

The set of regulatory interactions between genes, mediated by transcription factors, forms a species’ transcriptional regulatory network (TRN). By comparing this network with measured gene expression data, one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with fewer …

The Effect Of The Study Region On Gis Models Of Species Geographic Distributions And Estimates Of Niche Evolution; Preliminary Tests With Montane Rodents (Genus Nephelomys) In Venezuela, Ali Raza

Dissertations and Theses

Various niche-based techniques exist to model a species' potential geographic distribution in a Geographic Information Systems (GIS) framework. These models compare the environmental conditions of localities of a species' occurrence versus those of the overall study region. In addition to uses in areas such as macroecology and conservation biology, this approach has been applied recently to studies of niche evolution and historical biogeography. Definition of the study region is critical for all of these applications but has not been addressed previously. Here, I examine the effect of changes in the extent of the study region on potential distribution models of …

Using Geographically Structured Evaluations To Assess Performance And Transferability Of Ecological Niche Models For Species With Many Occurrence Records: A Test Using The Caribbean Spiny Pocket Mouse, Heteromys Anomalus, Aleksandarc Radosavljevi

Dissertations and Theses

No abstract provided.

The Impact Of Microclimate On Branch Colonization By Neotropical Cerambycid Beetles, Christina Lee

Dissertations and Theses

"Vertical stratification contributes to the great diversity of insects found in tropical rainforests. Due to differences in both biotic and abiotic factors, different strata of the forest provide different habitats for insects. A previous study in French Guiana revealed that wood-boring cerambycid beetles preferentially colonized branches at ground level in the dry season, but shifted to canopy level in the rainy season. The current beetle-rearing study was conducted to confirm the occurrence of this seasonal shift, explore possible causes, and to determine if similar microclimate conditions occurred at ground level in the dry season and the canopy level in the …

Role Of Drosophila Rap/Fzr (Cdh1) In Retinal Axon Targeting And Its Interactions With Loco, Liprin-A And Ras, Marta Gronska

Dissertations and Theses

The development of the wild type Drosophila compound eye involves stereotypical targeting of photoreceptor axons to the specific layers of the optic ganglion, medulla and lamina, in the third instar larvae. To test the hypothesis that ubiquitin ligases play an important role during retinal axon targeting we have examined the patterns of axon targeting in the developing eye of the retina aberrant in pattern (rap/fzr) mutants. Rap/Fzr is a homolog of mammalian Cdh1, an activator of anaphase promoting complex (APC), an E3 ubiquitin ligase. Previous work has shown that Rap/Fzr is required in cell cycle regulation, glia differentiation and pattern …