*PLEASE DO THE PRACTICE YOURSELF FIRST.
DO NOT READ THE REFERRED ARTICLES. WE WILL DISCUSS THE ANSWERS IN CLASS.
Week 1. Articles
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Practice 1: Fill in gaps with articles (a, an or the) or zero articles.
_ Lyme disease (Borrelia burgdorferi) and _ relapsing-fever (Borrelia hispanica) agents have _ distinct
infection courses, but both require _ cholesterol for _ growth. They acquire _ cholesterol from _
environment and process it to form _ cholesterol glycolipids that are incorporated onto their
membranes. To determine whether _ higher levels of _ serum cholesterol could enhance _ organ
burdens of _ B. burgdorferi and _ spirochetemia of _ B. hispanica in _ laboratory mice,
apolipoprotein E (apoE)-deficient and _ low-density lipoprotein receptor (LDLR)-deficient mice that
produce _ large amounts of _ serum cholesterol were infected with both _ spirochetes. Both _ apoEand LDLR-deficient mice infected with B. burgdorferi had _ increased number of _ spirochetes in _
joints and _ inflamed ankles compared with _ infected wild-type (WT) mice, suggesting that _
mutations in _ cholesterol transport that result in _ high serum cholesterol levels can affect _
pathogenicity of _ B. burgdorferi. In contrast, _ elevated serum cholesterol did not lead to _ increase
in _ spirochetemia of _ B. hispanica. In _ LDLR-deficient mice, _ course of _ infection was
indistinguishable from _ WT mice. However, _ infection of _ apoE-deficient mice with _ B. hispanica
resulted in _ longer spirochetemia and _ increased mortality. Together, these results argue for _
apoE deficiency, and not _ hypercholesterolemia, as _ cause for _ increased severity with _ B.
hispanica. _ Serum hyperlipidemias are _ common human diseases that could be _ risk factor for _
increased severity in _ Lyme disease.
Reference: Toledo, A. et. al. (2015) Hypercholesterolemia and ApoE deficiency result in severe
infection with Lyme disease and relapsing-fever Borrelia. PNAS, 112(17): 5491-5496.
*PLEASE DO THE PRACTICE YOURSELF FIRST.
DO NOT READ THE REFERRED ARTICLES. WE WILL DISCUSS THE ANSWERS IN CLASS.
Additional practice
Practice 2: Find nouns and determine the right articles that precede the nouns.
High expression of estrogen receptor α (ERα) is associated with poor prognosis that correlates
closely with cellular proliferation in breast cancer. However, exact molecular mechanism by which
ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates cell cycle
by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen (PCNA) and
proliferation-related Ki–67 antigen (Ki–67) to promote proliferation of MCF–7 cells. In addition, 17–
β–estradiol (E2) enhances ERα-induced proliferation of MCF–7 cells by stimulating expression of
PCNA and Ki–67. Knockdown of ERα significantly affects PCNA/Ki–67 and p53/p21 expression.
Furthermore, ERα inhibits transcriptional activity of p53/p21 in estrogen response elementdependent manner. More importantly, we provide new evidence that ERα mediates proliferation of
MCF–7 cells by up-regulating miR–17 to silence expression of p21. Thus, these data provide new
insights into underlying effect of ERα on breast cancer proliferation.
Reference: Liao, X-W et. al. (2014). Estrogen receptor α mediates proliferation of breast cancer
MCF–7 cells via a p21/PCNA/E2F1-dependent pathway. FEBS. J., 281(3): 927-942.
Practice 3: Find nouns and determine the right articles that precede the nouns.
Apolipoprotein E (Apo-E) is major cholesterol carrier that supports lipid transport and injury repair
in brain. APOE polymorphic alleles are main genetic determinants of Alzheimer disease (AD) risk:
individuals carrying ε4 allele are at increased risk of AD compared with those carrying more common
ε3 allele, whereas ε2 allele decreases risk. Presence of APOE ε4 allele is also associated with
increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal
ageing. Apo-E–lipoproteins bind to several cell-surface receptors to deliver lipids, and also to
hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic
dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and
clearance in brain, and have distinct functions in regulating brain lipid transport, glucose
metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we
describe current knowledge on Apo-E in CNS, with particular emphasis on clinical and pathological
features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβindependent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective
strategies for AD therapy by targeting Apo-E.
Reference: Liu, C-C. et. al. (2013) Apolipoprotein E and Alzheimer disease: risk, mechanisms and
therapy. Nat. Rev. Neurology, 9: 106-118.