Science - USA (2019-01-18)

242 18 JANUARY 2019 • VOL 363 ISSUE 6424 sciencemag.org SCIENCE

PHOTO: CLAUDIO GIOVANNI COLOMBO/ALAMY STOCK PHOTO

METALLOPROTEINS

A lanthanide secret

handshake

Most metal ions in biology

have distinct properties

determined by atomic

number and oxidation state.

However, some metals

in the lower rows of the

periodic table are notorious

for mimicking their lighter

cousins: Trivalent yttrium

and lanthanides, for example,

can replace divalent calcium

ions in some proteins. Cook

et al. determined the solu-

tion structure of a protein

that has evolved exquisite

selectivity for these heavier

ions over the lighter calcium.

Despite superficial similar-

ity to the calcium-binding

protein calmodulin, there

are large differences in the

overall protein structure,

and an additional carboxylic

acid ligand is likely crucial

for recognition of the heavier

ions. —MAF

Biochemistry 10.1021/acs.

biochem.8b01019 (2018).

PREGNANCY

Understanding

preeclampsia

Preeclampsia is character-

ized by the development of

hypertension and kidney

dysfunction during late stages

of pregnancy, and it is an

important cause of maternal

and fetal mortality. Quitterer

et al. found that increased

complex formation between

the G protein–coupled recep-

tors angiotensin II AT1 and

bradykinin B2 in vascular

smooth muscle cells triggered

preeclampsia in pregnant mice.

Evidence for the hyperactivity

of this heterodimer was also

found in vascular structures in

samples of placenta from preg-

nancies that had preeclampsia.

Using a small-molecule

inhibitor to target AT1-B2

receptor signaling prevented

preeclampsia in mice. Initial

data in patients with symptoms

of preeclampsia indicate that

this is an avenue for treatment

options. —GKA

Cell 176 , 318 (2019).

IN OTHER JOURNALS

et al. used in vivo neural calcium
imaging in freely behaving mice.
They identified brain circuits
that respond to pain and directly
tested their causal role in moti-
vational behaviors associated
with acute and chronic pain.
—PRS
Science, this issue p. 276

CILIA

Assembly of the ciliary

microtubule doublet

The cilium is a conserved
organelle that is crucial for
motility as well as for sensing
the extracellular environment.
Its core structure is charac-
terized by nine microtubule
doublets (MTDs). The mecha-
nisms of MTD assembly are
unclear. Schmidt-Cernohorska
et al. developed an assay to
reconstitute MTD assembly in
vitro. Tubulin carboxyl-terminal
tails played a critical inhibi-
tory role in MTD formation.
Molecular dynamics revealed
that carboxyl-terminal tails of
the A11 microtubule protofila-
ment regulated MTD initiation.
Furthermore, live-cell imaging
showed an unexpected bidirec-
tional isotropic elongation of the
MTD. —SMH
Science, this issue p. 285

IMMUNOTHERAPY

Serotherapy treats a

transplant hurdle

Cytomegalovirus (CMV)
infection and reactivation are
common and potentially fatal
complications after bone mar-
row or hematopoietic stem cell
transplantation (BMT). Martins
et al. developed faithful pre-
clinical murine models of CMV
reactivation following BMT and
found that humoral immunity
can prevent this process (see
the Perspective by Alegre). After
BMT, antiviral antibodies that
would have kept CMV at bay
dwindle because host plasma
cells are ablated and the donor
B cell pool reconstitutes poorly.
CMV reactivation was prevented
by transferring antibody-
containing immune serum.

Such a therapeutic strategy

would avoid some limitations

of cellular therapies for BMT

patients. —STS

Science, this issue p. 288;

see also p. 232

FIBROSIS

When cell adhesion

promotes fibrosis

Inflammatory macrophages

produce the c ytokine trans-

forming growth factor–b

(TGF-b), which induces the

activation of fibroblasts into

myofibroblasts that secrete

extracellular matrix and

promote fibrosis. Lodyga et

al. found that the adhesion

protein cadherin-11 (CDH11)

was enriched at contact points

between macrophages and

myofibroblasts in fibrotic lung

tissues from mice and human

patients. CDH11-mediated

adhesion between macro-

phages and lung fibroblasts

triggered the activation of fibro-

blasts into myofibroblasts and

targeted macrophage-produced

TGF-b to myofibroblasts, creat-

ing a self-sustaining profibrotic

niche. —AV

Sci. Signal. 12 , eaao3469 (2019).

TUMOR IMMUNOLOGY

Neoantigen reactivity

Increased frequencies of intra-

tumoral CD4+ regulatory T cells

(Tregs) have typically been asso-

ciated with more-rapid tumor

progression, but the antigen

specificity of these Tregs within

tumors is not well understood.

Ahmadzadeh et al. character-

ized the T cell receptor (TCR)

repertoire of intratumoral Tregs

from patients with metastatic

melanoma, gastrointestinal,

and ovarian cancers. These

Tregs had a unique TCR rep-

ertoire different from other

intratumoral CD4+ T cells, and

dominant TCRs were specific

to tumors and neoantigens.

Similar cells were also found in

the periphery, indicating that

these Tregs may be expanding

from both compartments.

—CNF

Sci. Immunol. 4 , eaao4310 (2019).

RESEARCH | IN SCIENCE JOURNALS

Edited by Caroline Ash

and Jesse Smith

Published by AAAS