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               <mods:identifier type="citation">PLoS Genet. 2015; 11(3):e1005120</mods:identifier>
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               <mods:abstract>Anaplasma phagocytophilum is an emerging pathogen that causes human&#xd;
granulocytic anaplasmosis. Infection with this zoonotic pathogen affects&#xd;
cell function in both vertebrate host and the tick vector, Ixodes&#xd;
scapularis. Global tissue-specific response and apoptosis signaling&#xd;
pathways were characterized in I. scapularis nymphs and adult female&#xd;
midguts and salivary glands infected with A. phagocytophilum using a&#xd;
systems biology approach combining transcriptomics and proteomics.&#xd;
Apoptosis was selected for pathway-focused analysis due to its role in&#xd;
bacterial infection of tick cells. The results showed tissue-specific&#xd;
differences in tick response to infection and revealed differentiated&#xd;
regulation of apoptosis pathways. The impact of bacterial infection was&#xd;
more pronounced in tick nymphs and midguts than in salivary glands,&#xd;
probably reflecting bacterial developmental cycle. All apoptosis&#xd;
pathways described in other organisms were identified in I. scapularis,&#xd;
except for the absence of the Perforin ortholog. Functional&#xd;
characterization using RNA interference showed that Porin knockdown&#xd;
significantly increases tick colonization by A. phagocytophilum.&#xd;
Infection with A. phagocytophilum produced complex tissue-specific&#xd;
alterations in transcript and protein levels. In tick nymphs, the&#xd;
results suggested a possible effect of bacterial infection on the&#xd;
inhibition of tick immune response. In tick midguts, the results&#xd;
suggested that A. phagocytophilum infection inhibited cell apoptosis to&#xd;
facilitate and establish infection through up-regulation of the JAK/STAT&#xd;
pathway. Bacterial infection inhibited the intrinsic apoptosis pathway&#xd;
in tick salivary glands by down-regulating Porin expression that&#xd;
resulted in the inhibition of Cytochrome c release as the anti-apoptotic&#xd;
mechanism to facilitate bacterial infection. However, tick salivary&#xd;
glands may promote apoptosis to limit bacterial infection through&#xd;
induction of the extrinsic apoptosis pathway. These dynamic changes in&#xd;
response to A. phagocytophilum in I. scapularis tissue-specific&#xd;
transcriptome and proteome demonstrated the complexity of the tick&#xd;
response to infection and will contribute to characterize gene&#xd;
regulation in ticks.</mods:abstract>
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               <mods:subject>
                  <mods:topic>FATTY-ACID SYNTHASE</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>GENE-EXPRESSION</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>QUANTITATIVE PROTEOMICS</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>HUMAN&#xd;
NEUTROPHILS</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>CANCER-CELLS</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>RNA-SEQ</mods:topic>
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               <mods:subject>
                  <mods:topic>INFECTION</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>INHIBITORS</mods:topic>
               </mods:subject>
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                  <mods:title>Systems Biology of Tissue-Specific Response to Anaplasma phagocytophilum&#xd;
Reveals Differentiated Apoptosis in the Tick Vector Ixodes scapularis</mods:title>
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