1205-B 4 SEPTEMBER 2020 • VOL 369 ISSUE 6508 sciencemag.org SCIENCE
RESEARCH
CELL BIOLOGY
Reconstituting
autophagosome nucleation
To stay healthy, our cells must
constantly dispose of harm-
ful material. Autophagy, or
self-eating, is an important
mechanism to ensure the clear-
ance of bulky material. Such
material is enwrapped by cellular
membranes to form autophago-
somes, the contents of which are
then degraded. The formation of
autophagosomes is a compli-
cated process involving a large
number of factors. How they act
together in this process is still
enigmatic. Sawa-Makarska et al.
recapitulated the initial steps of
autophagosome formation using
purified autophagy factors from
yeast. This approach elucidated
some of the organizational
principles of the autophagy
machinery during the assembly
of autophagosomes. —SMH
Science, this issue p. 1206
PHYSIOLOGY
Body clock resilience
The body clock, or circadian
rhythm, which couples activi-
ties and homeostatic processes
to daylight, is different in men
and women. Evidence suggests
that women have higher peaks
of activity during earlier parts
of the day than men, in-line with
children, and that they are more
resilient to shifts in daylight (as
would occur when changing
time zones or with shift work).
In a Perspective, Anderson and
FitzGerald discuss the possible
mechanisms and implications
of different circadian rhythms in
men and women and how these
may affect health. —GKA
Science, this issue p. 1164
REGENERATION
Regulatory elements of
fish regeneration
Some animals regenerate exten-
sively, whereas others, such as
mammals, do not. The reason
behind this difference is not
clear. If the genetic mechanisms
driving regeneration are evolu-
tionarily conserved, the study of
distantly related species that are
subjected to different selective
pressures could identify distin-
guishing species-specific and
conserved regeneration-respon-
sive mechanisms. Zebrafish and
the short-lived African killifish
are separated by ~230 million
years of evolutionary distance
and, as such, provide a biological
context to elucidate molecular
mechanisms. Wang et al. identify
both species-specific and evolu-
tionarily conserved regeneration
programs in these fish. They also
provide evidence that elements
of this program are subjected to
evolutionary changes in verte-
brate species with limited or no
regenerative capacities. —BAP
Science, this issue p. 1207NEUROSCIENCE
Sleep and basal
forebrain activity
Different patterns of neural
activity in the brain control the
sleep-wake cycle. However, how
this activity contributes to sleep
homeostasis remains largely
unknown. Adenosine in the
basal forebrain is a prominent
physiological mediator of sleep
homeostasis. Using a newly
developed indicator, Peng et al.
monitored adenosine con-
centration in the mouse basal
forebrain. There was a clear
correlation with wake state and
REM sleep. Activity-dependent
release of adenosine could also
be elicited after optogenetic
stimulation of basal forebrain
glutamatergic, but not choliner-
gic, neurons. These findings offer
new insights into how neuronal
activity during wakefulnesscontributes to sleep pressure
through the release of sleep-
inducing factors. —PRS
Science, this issue p. 1208CORONAVIRUS
Immune profiling of
COVID-19 patients
Coronavirus disease 2019
(COVID-19) has affected mil-
lions of people globally, yet how
the human immune system
responds to and influences
COVID-19 severity remains
unclear. Mathew et al. present a
comprehensive atlas of immune
modulation associated with
COVID-19. They performed high-
dimensional flow cytometry of
hospitalized COVID-19 patients
and found three prominent
and distinct immunotypes that
are related to disease sever-
ity and clinical parameters.
Arunachalam et al. report a sys-
tems biology approach to assess
the immune system of COVID-19
patients with mild-to-severe
disease. These studies provide
a compendium of immune cell
information and roadmaps for
potential therapeutic interven-
tions. —PNK
Science, this issue p. 1209, p. 1210PROTEIN DESIGN
A new tool in the protein
design toolbox
Protein design can compute pro-
tein folds from first principles.
However, designing new proteins
that are functional remains
challenging, in part because
designing binding interactions
requires simultaneous optimiza-
tion of protein sequence and
protein-ligand conformation.
Polizzi and DeGrado designed
proteins from scratch that bind
a small-molecule drug (see the
Perspective by Peacock). They
introduced a new structural ele-
ment called a van der Mer (vdM),
which tracks the orientation
of a chemical group relative to
the backbone of a contactingresidue. Assuming proteins
bind ligands using interactions
similar to intraprotein packing,
they determined statistically
preferred vdMs from a large set
of structures in the Protein Data
Bank. By including weighted
vdMs in their computations,
they designed two of six de novo
proteins that bind the drug
apixaban. A drug-protein x-ray
crystal structure confirmed the
designed model. —VV
Science, this issue p. 1227;
see also p. 1166METROLOGY
A very precise ratio
The value of the ratio of the
masses of the proton and the
electron has a bearing on the
values of other physical con-
stants. This ratio is known to a
very high precision. Patra et al.
improved this precision even
further by measuring particular
frequencies in the rovibrational
spectrum of the hydrogen
deuteride molecular ion (HD+)
(see the Perspective by Hori).
To reach this high precision,
the researchers placed the HD+
molecules in an ion trap and sur-
rounded them by beryllium ions.
The cold beryllium ions then
helped cool the HD+ molecules,
making the HD+ spectral lines
narrow enough that the proton-
electron mass ratio could be
extracted by comparison with
theoretical predictions. —JS
Science, this issue p. 1238;
see also p. 1160CORONAVIRUS
The spread of
SARS-CoV-2 in Brazil
Brazil has been hard-hit by
the severe acute respiratory
syndrome coronavirus 2 (SARS-
CoV-2) pandemic. Candido et al.
combined genomic and epidemi-
ological analyses to investigate
the impact of nonpharmaceuti-
cal interventions (NPIs) in the
country. By setting up a network
of genomic laboratories usingEdited by Michael FunkALSO IN SCIENCE JOURNALS
Published by AAAS