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+\begin_body
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+
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+\begin_layout Title
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+Current Studies on Molecular Mechanisms of Iron Homeostasis in Rhinoceroses
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+\end_layout
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+
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+\begin_layout Author
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+Rose Linzmeier, Ph.D.1
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+Department of Pulmonary and Critical Care Medicine and Department of Pathology
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+ and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095
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+
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+ Ryan Thompson2
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+Department of Molecular and Experimental Medicine, The Scripps Research
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+ Institute, La Jolla, CA 92037
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+\end_layout
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+
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+\end_inset
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+
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+ Sarah LaMere, D.V.M
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+\begin_inset ERT
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+status open
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+
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+\end_layout
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+
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+\end_inset
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+
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+ Pauline Lee, Ph.D.
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+\begin_inset ERT
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+status open
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+
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+\end_inset
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+
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+ Elizabeta Nemeth, Ph.D.
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+\begin_inset ERT
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+status open
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+
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+
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+
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+\end_inset
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+
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+ Tomas Ganz, M.D., Ph.D.
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+\begin_inset ERT
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+status open
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+
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+
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+\end_inset
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+
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+ Donald E.
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+ Paglia, M.D.
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+\begin_inset Foot
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+status collapsed
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+
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+UCLA Hematology Research Laboratory, Department of Pathology and Laboratory
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+ Medicine, UCLA School of Medicine, Los Angeles, CA 90095
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+\end_layout
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+
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+\end_inset
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+
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+
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+\begin_inset Note Note
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+status collapsed
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+
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+\begin_layout Plain Layout
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+Look into https://tex.stackexchange.com/q/34746/5654
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+\end_layout
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+
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+\end_inset
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+
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+
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+\end_layout
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+
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+\begin_layout Date
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+2013
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+\end_layout
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+
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+\begin_layout Standard
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+Iron storage disease (ISD) is a hazardous and clinically underappreciated
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+ condition commonly acquired by exotic wildlife species when displaced from
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+ their natural habitats and confined for even short periods under artificial
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+ conditions.
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+ An international symposium recently reviewed and validated evidence that
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+ African black and Sumatran rhinoceroses invariably develop progressive
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+ ISD commensurate with their times in captivity, whereas African white and
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+ Indian rhinoceroses do not
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "SpecialSupplement2012"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ Since vulnerability to ISD is a species-wide characteristic, it is likely
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+ to have a genetic basis possibly reflecting evolutionary adaptions to differenc
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+es in iron bioavailability between browser and grazer diets.
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+
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+\end_layout
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+
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+\begin_layout Standard
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+As a biologically essential element that is also highly toxic in excess,
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+ iron is exquisitely regulated by molecular mechanisms primarily focused
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+ on interactions between the peptide hepcidin, (the principal iron-regulatory
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+ hormone), and its receptor ferroportin, (the sole channel for egress of
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+ intracellular iron into plasma)
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "nemethRegulationIronMetabolism2006"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ Iron-regulatory gene sequences from both ISD-susceptible and non-susceptible
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+ species were compared to search for possible molecular differences.
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+ DNA was extracted from peripheral blood samples from all four available
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+ rhinoceros species, and genes encoding hepcidin and ferroportin, as well
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+ as modulators hemojuvelin, transferrin receptor 2, and HFE protein, were
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+ cloned and analyzed by PCR amplification.
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+ Over half of the DNA sequences of these five genes have now been determined
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+ without identifying any that could account for disparities in iron loading
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+ among the species.
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+ Evaluation of the remaining sequences continues, as do studies to determine
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+ the responsiveness of rhinoceros ferroportin to hepcidin modulation and
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+ quantitative levels of hepcidin expression
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "r.linzmeierRegulationIronBalance2008"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+
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+\end_layout
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+
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+\begin_layout Standard
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+In addition, liver and spleen mRNA sequences from African black and white
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+ rhinoceroses were assembled using Trinity RNA-Seq software
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "grabherrFulllengthTranscriptomeAssembly2011"
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+literal "false"
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+
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+\end_inset
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+
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+ and compared with human sequences using the SIFT algorithm
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "kumarPredictingEffectsCoding2009"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ Candidate single-nucleotide polymorphisms were independently validated
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+ by genomic sequencing.
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+ Mutations were found in four genes that may be associated with primary
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+ iron disorders or hemolytic anemia in black rhinoceroses: SLC28a2, EPB41,
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+ MTF1, and STEAP4
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "r.linzmeierRegulationIronBalance2013"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ The functional consequences of these mutations are being determined.
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+\end_layout
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+
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+
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