SCIENCE sciencemag.org 16 AUGUST 2019 • VOL 365 ISSUE 6454 654-Cstandard hyperfractionated
EGFR TKI treatment (HyperTKI),
is a problem that has driven
the development of next-
generation inhibitors. Liu et al.
describe the improved efficacy
of hypofractionated EGFR TKI
treatment (HypoTKI) relative to
HyperTKI in triggering antitumor
T cell responses and prevent-
ing relapse in a TKI-sensitive
syngeneic murine tumor model
through a mechanism involving
immune signaling pathways.
Coadministration of HypoTKI
with an immunotherapy anti-
body further improved antitumor
responses and reduced tumor
relapse, thus suggesting that
this combined therapy may be a
potential alternative to existing
treatment regimens. —CNF
Sci. Immunol. 4 , eaav6473 (2019).
ALZHEIMER’S DISEASE
An appetite for memory
The hippocampus serves a
critical role in memory forma-
tion and cognition. Hippocampal
lesions are among the earliest
changes in Alzheimer’s disease
(AD); however, the molecular
mechanisms responsible for
these alterations remain unclear.
Using autoptic brain samples
from patients with AD and a
mouse model of AD, Tian et al.
show that in the hippocampus,
pathologic b-amyloid directly
binds and inhibits the receptor
for the “hunger hormone” ghrelin
(GHSR1a). In the animal model,
the binding blocked the GHSR1a-
mediated dopamine receptor
D1 (DRD1) activation, leading to
synaptic plasticity impairments
and memory loss. Simultaneous
pharmacological activation of
GHSR1a and DRD1 rescued
synaptic plasticity and spatial
memory in AD mice. —MM
Sci. Transl. Med. 11 , eaav6278 (2019).
NEUROSCIENCE
Sharp-wave ripples
in the hippocampus
What are the brain mecha-
nisms responsible for episodic
memory retrieval? Norman et
al. investigated epilepsy patients
who had electrodes implanted
in the hippocampus and a
variety of cortical areas. Using
a visual learning paradigm, they
examined the temporal relation-
ship between the incidence of
hippocampal sharp-wave ripples
and recall. Effective encoding of
visual information was associ-
ated with higher incidence of
ripples. Successful recall was
preceded by an increased prob-
ability of ripples, which were
also associated with transient
reemergence of activation pat-
terns in higher visual cortical
areas. Hippocampal ripples may
thus boost recollections during
episodic memory retrieval.
—PRS
Science, this issue p. 657