Science - USA (2022-03-04)

SCIENCE science.org

IMAGE: KURT DAHLSTROM

in the United States, the study

reports statistically significant

differences in the electroen-

cephalography brain scans of

1-year-old infants from the two

groups. The study is ongoing

and will follow these families

to determine whether the

observed differences between

the two groups will persist and

lead to cognitive and behav-

ioral differences later on. —YY

Proc. Natl. Acad. Sci. U.S.A. 119 ,

e2115649119 (2022).

OBESITY

Unfolding the sequelae

of obesity

Obesity and type 2 diabetes

are increasingly common

worldwide and are associ-

ated with numerous health

complications. Given the

complexity of these metabolic

illnesses, it is not surpris-

ing that multiple signaling

pathways are involved and the

connections are not always

straightforward. For example,

activation of the unfolded pro-

tein response can be protective

or detrimental depending on

the degree and duration of

activation. Madhavan et al.

have untangled some of the

complexities of the unfolded

protein response signaling in

mouse models, then attempted

to deflect the response using a

small-molecule compound. The

treatment improved glucose

metabolism and reduced the

accumulation of fat in the

animals’ livers, indicating its

potential for therapeutic appli-

cations. —YN

Nat. Commun. 13 , 608 (2022).

CANCER IMMUNOLOGY

Sweet spot for TCR

The T cell receptor (TCR) is a

complex on the surface of T

lymphocytes that participates

in the activation of antitumor T

cell immune responses. During

acute infections, high-affinity

interactions with pathogen anti-

gens trigger T cell expansion,

but in cancer, TCR affinity to

tumor self-antigens may be low.

Shakiba et al. examined how

different TCR signal strengths

affected the ability of a subset

of T cells called CD8+ T cells to

control tumors in mice. Weak

TCR–tumor antigen interactions

led to ineffective cancer cell kill-

ing, whereas strong TCR–tumor

antigen engagement drove T

cells into a nonfunctional state.

However, immunogenic tumor

neoantigens from human mela-

noma and lung cancer mostly

have intermediate TCR affinity.

Subsequent fine-tuning of the

TCR signal to the intermedi-

ate “sweet spot” improved the

ability of T cells to elicit tumor

cell clearance and may provide

avenues for improved cancer

immunotherapies. —PNK

J. Exp. Med. 219 , e20201966 (2022).

MACHINE LEARNING

Exploring organo-

phosphorus ligands

Machine learning (ML) has

become a mainstream tool in

the development of numerous

algorithms for virtual chemi-

cal space exploration and is

increasingly being applied

to more and more complex

chemical systems. Gensch et

al. present a comprehensive

ML-based discovery plat-

form to study the property

space of organophosphorous

(III) ligands (actively used

in homogeneous catalysis),

which was able to predict 190

physicochemical descriptors

for more than 300,000 new

ligands. Their platform could

be used for the inverse design

of homogeneous catalysts

and could be adapted to other

classes of ligands in the future.

—YS

J. Am. Chem. Soc. 144 , 1205 (2022).

GENDER GAP

The manly art

of self-promotion

Gender wage gaps may have

roots in men being more self-

promoting than women. Exley

and Kessler had more than

4000 adults perform tasks

and then rate their subjective

performance on a scale. Men

judged their math and science

performance more favorably

than did equally performing

women regardless of whether

participants were first told how

they actually scored and if they

were first told that the self-

evaluations were to be shared

with potential employers or

kept private. Men and women

rated performance similarly

for other participants and for

themselves on a test of verbal

skills. Similar gaps were seen in

more than 10,000 middle- and

high-school-aged participants.

—BW

Q. J. Econ. https://doi.org/

10.1093/qje/qjac003 (2022).

4 MARCH 2022 • VOL 375 ISSUE 6584 989

SYMBIOSIS

Personalized fungal detox

B

acteria in the wild use a slew of small molecules to

help them earn a living. Phenazines are redox-

active bacterial products that are widespread in the

environment and are harmful to fungi but not to all

bacteria. Dahlstrom and Newman found in crop-

land soils that the bacterium Paraburkholderia edwinii

protected cohabiting Aspergillus fungi from the toxic

effects of phenazine-1-carboxylic acid (PCA). Aggregates

of bacteria within a colony of Aspergillus soaked up the

PCA, whereas the fungus promoted acidic reducing

conditions that limited the toxicity of the sequestered

PCA. Aggregation in P. edwinii is regulated by the

transcriptional repressor HrcA, which is found in many

bacteria with fungal partners. HrcA could be as important

in establishing interkingdom microbial communities on

coral reefs or in the human gut as it is in the rhizosphere.

—CA Curr. Biol. 32 , 275 (2021).

The fungus Aspergillus finds refuge from toxins within colonies

of the bacterium Paraburkholderia edwinii.