<p>by Anurag Das, Irma Magaly Rivas-Serna, Ankur Kumar, Lakpa Sherpa, Kerui Huang, Hia Kalita, Marlene Dorneich-Hayes, Ruiqi Liu, Vera C. Mazurak, John P. Vaughen, Hua Bai</p>
Peroxisomes are critical organelles that detoxify cellular waste while also catabolizing and anabolizing lipids. How peroxisomes coordinate protein import and support metabolic functions across complex tissues and timescales remains poorly understood in vivo. Using the <i>Drosophila</i> brain, we discover a striking enrichment of peroxisomes in the neuronal soma and the cortex glia that enwrap them. Unexpectedly, import of peroxisomal proteins into cortex glia, but not neurons, oscillated across time and peaked in the early morning. Rhythmic peroxisomal import in cortex glia autonomously required the circadian clock and Peroxin 5 (Pex5; peroxisomal biogenesis factor 5 homolog), with import persistently elevated in clock mutants. Notably, reducing <i>Pex5</i> in cortex glia, but not neurons, caused hyperactivity and reduced total sleep. Moreover, brain lipid metabolism was dramatically altered upon <i>Pex5</i> knockdown, with glia impacting sphingolipids and triacylglycerols, and neurons impacting phospholipids. The cell-type specificity of these Pex5 phenotypes highlights unique roles for peroxisomal import in both sleep and lipid metabolism in the brain.
Science Journals
<p>by Chloé Guillaume, Elisa Galliano</p>
Smells linked to joyful childhood events trigger vivid memories in adulthood, yet the mechanism behind their formation has remained elusive. A new PLOS Biology study shows that neurons generated around birth play a key role in encoding these olfactory memories.
Smells linked to joyful childhood events trigger vivid memories in adulthood, yet the mechanism behind their formation has remained elusive. This Primer explores a new study in PLOS Biology that shows that neurons generated around birth play a key role in encoding these olfactory memories.
Physical activity is believed to positively influence brain health and cognition and is considered a modifiable lifestyle factor that may protect against cognitive decline and neurodegeneration. In this observational study, we investigated the cross-sectional and longitudinal effects of self-reported total and moderate-to-vigorous physical activity on cognitive scores on the Trail Making Test (TMT-A and TMT-B), hippocampal volume, and Brain Age Gap Estimate (BrainAGE) in a large population-based cohort from the LIFE-Adult Study (n=2576). Furthermore, we examined the effect of objectively measured physical activity on brain structure in a subgroup with available accelerometry data (n=227). Multiple linear regression analyses did not show any positive effects of self-reported or objectively measured physical activity on hippocampal volume or processing speed and executive function. Longitudinal path analyses suggested a potential for reverse causation, where a higher BrainAGE at baseline was associated with lower physical capacity at follow-up. Additionally, we observed an age-related bias in the self-reporting of physical activity, indicating that older individuals tend to overestimate their level of activity. Future interventions targeting middle-aged adults may be necessary to raise awareness of potential misperception and encourage increased physical activity.
<p>by Yanzhu Ji, Lei Wu, Dongming Li, Shaohong Feng, Qi Fang, Ying Xiong, Yongbin Chang, Jacob C. Cooper, Xin Yu, Kai Zhang, Shiyu Tang, Huishang She, Huan Wang, Dezhi Zhang, Gang Song, Ping Fan, Jiaogen Zhou, Liang Ma, Yanhua Qu, Chenxi Jia, Catherine Sheard, James Andrew DeWoody, Joseph A. Tobias, Guojie Zhang, Weiwei Zhai, Fumin Lei</p>
As a hallmark of avian ecological innovation, powered flight has fundamentally shaped diverse aspects of birds. The energy demand of flight may have mutagenic impacts on genomes, influencing how fast genomes evolve. However, the relationship between flight, metabolism, and evolutionary rates remains relatively underexplored. Leveraging 363 newly available avian genomes from >90% of avian families, we quantified three distinct types of genomic evolutionary rates to capture a broad spectrum of mutational processes. By combining four flight-related traits and three metabolic metrics, we uncovered significant associations between flight style, metabolism, and multiple evolutionary rates. Next, using a causal inference framework, we demonstrated that metabolism accounted for 43.3% of the total effect between flight and evolutionary rate, underscoring its key role. Together, our findings establish a robust connection between flight, metabolism, and evolutionary rates, offering new insights into how key innovations and associated phenotypes shape the tempo of genome evolution.
<p>by Bipin Kumar Tripathi, Zhenru Zhou, Kenneth D. Irvine</p>
Proper organ shape is critical for function. The <i>Drosophila</i> wing normally adopts an elongated shape, but mutations in the Dachsous-Fat pathway result in rounder wings. The mechanism by which this occurs has remained unclear. Here, we show that Ds-Fat signaling shapes the wing during the larval stage, rather than during pupal development when morphogenetic rearrangements transform the developing wing disc into the adult wing. We further find that Ds-Fat alters tissue-wide stresses in the wing disc, and genetic manipulations that reduce cytoskeletal tension result in rounder wings, whereas increasing cytoskeletal tension produces more elongated wings. Reduced tension is also associated with less oriented growth during development. Notably, increased cytoskeletal tension partially rescues the rounder shape caused by <i>ds</i> knockdown. These results reveal a previously unrecognized mechanism by which Ds-Fat signaling determines wing shape, involving regulation of tissue tension to orient growth and shape the wing primordia during larval development.
<p>by Lucas M. Martini, Anna Bognár, Rufin Vogels, Martin A. Giese</p>
Social interactions are essential for survival in primates, relying on both facial expressions and body signals. The accurate characterization of these signals is critical for understanding the neurocomputational mechanisms underlying social communication. While previous work has focused on recognizing monkey behavior, a causal and direct manipulation of individual cues strongly benefits from believable, dynamic body avatars—analogous to those successfully developed for faces. Creating lifelike monkey avatars with realistic body motion, however, is challenging. Acquiring sufficiently accurate movement data for animation with marker-based motion capture is impractical, and markerless tracking methods require extensive manual labeling. To address this, we developed MacAction, a realistic macaque body avatar animated from multi-camera markerless tracking data. Our method reconstructs accurate trajectories for a large number of keypoints, as required for the 3D animation of realistic body models. The entire time course of individual actions is captured using only two labeled keyframes per second, with performance further validated on a large-scale human multi-view dataset. We assessed the animation quality of our dynamic avatar in a free-viewing experiment with eight macaque observers for single macaque actions, where fixation behavior was indistinguishable between our animations and matched real videos. Moreover, by systematically varying the realism of the avatar, we found an uncanny valley effect in macaque body perception, similar to that previously described in both humans and macaque faces. These findings support the commonalities of social vision across primate species, providing a foundation for controlled experiments aimed at clarifying the detailed neurocomputational mechanisms of social body perception in primates.
<p>by Jules Dejou, Anna Athanassi, Théo Brunel, Marc Thevenet, Anne Didier, Nathalie Mandairon</p>
Olfactory childhood memories are particularly important for forming one’s identity. However, we don’t know how they exert their privileged influence and shape brain structure. To address this, we modeled childhood olfactory memory in mice based on a human survey indicating that our earliest olfactory memory arises from repeated positive experiences paired with a pleasant odorant. Accordingly, mice were exposed during childhood to an attractive odorant in a playful environment. In adulthood, memory recall relied on neonatal-born granule cells (GCs) in the olfactory bulb, as their optogenetic silencing impaired retrieval, and on increased functional connectivity in the reward system. With age, memory persistence depended on re-exposure to the childhood odorant and was associated with the disengagement of neonatal-born GCs, alongside with strengthened limbic functional connectivity. Together, these findings identify neonatal neurons as a key substrate for encoding childhood olfactory memory and reveal dynamic reorganization of brain networks supporting its long-term significance.
This important study provides solid evidence that early childhood malaria exposure affects the development of antibody responses to unrelated pathogens and vaccine-derived antigens in Kenyan children. The findings are of major public health importance and limitations of the observational study design are properly acknowledged.
https://doi.org/10.7554/eLife.107820.3.sa0Important: Findings that have theoretical or practical implications beyond a single subfield
- Landmark
- Fundamental
- Important
- Valuable
- Useful
Solid: Methods, data and analyses broadly support the claims with only minor weaknesses
- Exceptional
- Compelling
- Convincing
- Solid
- Incomplete
- Inadequate
During the peer-review process the editor and reviewers write an eLife Assessment that summarises the significance of the findings reported in the article (on a scale ranging from landmark to useful) and the strength of the evidence (on a scale ranging from exceptional to inadequate). Learn more about eLife Assessments
Chronic malaria exposure has been proposed to modulate immune function, but its long-term effects on antibody-mediated responses to unrelated pathogens remain poorly defined. Whether these effects persist beyond periods of active infection and how early-life exposure shapes humoral immunity over time is not well understood.
We leveraged a natural experiment in coastal Kenya – where two regions (Junju and Ngerenya) diverged sharply in malaria transmission from around 2004 – to evaluate the long-term immunological consequences of malaria exposure in childhood. Using a protein microarray platform, we measured IgG responses to vaccine and pathogen antigens in 123 children sampled longitudinally over a 15-year period. Active weekly malaria surveillance enabled precise reconstruction of individual exposure histories.
IgG responses to Plasmodium falciparum apical membrane antigen 1 (AMA1) tracked closely with clinical malaria episodes, confirming the ability of the microarray platform …
The American College of Physicians (ACP) released a statement expressing concern about an executive order directing the US Centers for Disease Control and Prevention (CDC) to alter the childhood vaccine schedule.
This Medical News article discusses a new American Heart Association scientific statement on the role of physical activity in obesity care.
In Reply We thank Dr Yu and colleagues for their thoughtful commentary on our recent article addressing perinatal HIV management and infant feeding. Their emphasis on the postpartum period as an evolving and clinically distinct phase is both timely and important, and we appreciate the opportunity to expand on this critical aspect of care.
The conduct of randomized clinical trials (RCTs) is often a large-scale endeavor, with the potential to impact patients, clinicians, health care systems, and even the communities in which they are carried out. The effects of trials on participants may flow through the randomized study treatments or through other pathways, for example, by inducing changes to aspects of care separate from the randomized treatments. These effects may be beneficial (eg, participants may receive more careful evaluation, additional diagnostic studies, closer follow-up, or earlier detection of complications) or they may be harmful (eg, inconvenience or financial costs).
The room smells like pennies and plastic. Someone wipes gel from his ribs while his daughter still stands with hands on the rail, waiting for the monitor to change its mind. Outside, the hallway laughs— a coffee joke, a shift trade— and the day keeps walking past this door.
A new diffusion MRI approach offers a glimpse of the anomalies of cellular architecture underlying basal ganglia degeneration in Huntington’s disease.
The US Food and Drug Administration (FDA) released a warning advising consumers against using over-the-counter skin lightening products, which may contain high levels of mercury or hydroquinone.
This Perspective discusses female biology and resilience regarding Alzheimer disease despite pathologic risk.
This randomized clinical trial compares whether the addition of zoledronic acid to teriparatide compared with standard treatment reduces fractures among adults with osteogenesis imperfecta.
Elucidating the neuronal circuits that govern appetite requires precise, high-resolution monitoring of the microstructure of solid food consumption, a need unmet by existing tools, which are either costly or lack the temporal resolution to align feeding events with neuronal activity. To overcome this, we developed the Crunchometer, a low-cost, open-source acoustic system that uses computational algorithms to generate high-resolution feeding ethograms from the sounds produced during solid food consumption. Validation across energy states (hunger/satiety) confirmed its sensitivity to changes in feeding microstructure, and the system reliably detected semaglutide-induced suppression of intake and reduced preference for a high-fat diet. Leveraging its seamless integration with in vivo recordings in freely behaving mice, we paired the Crunchometer with lateral hypothalamus (LH) electrophysiology to identify ‘meal-related’ neurons that track entire meals rather than individual bouts. Calcium imaging further revealed that distinct subsets of LH GABAergic and glutamatergic neurons were tuned to feeding only, to licking only, or to both behaviors. Thus, LH neuronal ensembles differentially encode the consumption of solid food versus liquid sucrose. These findings demonstrate that the Crunchometer is a robust, accessible platform for dissecting the neural correlates of feeding behavior at the resolution of a single bite.
Nucleic acid aptamers hold promise for clinical applications, yet understanding their molecular binding mechanisms to target proteins, and efficiently optimizing their binding affinities, remain challenging. Here, we present CAAMO (<i>C</i>omputer-<i>A</i>ided <i>A</i>ptamer <i>M</i>odeling and <i>O</i>ptimization), which integrates in silico aptamer design with experimental validation to accelerate the development of aptamer-based RNA therapeutics. Starting from the sequence information of a reported RNA aptamer, Ta, for the SARS-CoV-2 spike protein, our CAAMO method first determines its binding mode with the spike protein’s receptor binding domain (RBD) through a multi-strategy computational approach. We then optimize its binding affinity via structure-based rational design. Among the six designed candidates, five were experimentally verified and exhibited enhanced binding affinities compared to the original Ta sequence. Furthermore, we directly compared the binding properties of the RNA aptamers to neutralizing antibodies and found that the designed aptamer Ta<sup>G34C</sup> demonstrated a comparable binding affinity to the RBD compared to the representative neutralizing antibodies analyzed in this study. This highlights its potential as an alternative to existing COVID-19 antibodies. Our work provides a robust approach for the efficient design of a relatively large number of high-affinity aptamers with complicated topologies. This approach paves the way for the development of aptamer-based RNA diagnostics and therapeutics.
Schlegel J, Denay G, Wink R, Pinto KG, Stahl Y, Schmid J, Blümke P, Simon RGW. 2021. Control of Arabidopsis shoot stem cell homeostasis by two antagonistic CLE peptide signalling pathways. eLife 10:e70934. doi: 10.7554/elife.70934.
Published 13 October 2021
We noticed that the reporter line used to investigate the number of WUSCHEL-expressing cells in Figure 7 was unstable and mislabelled as “pWUS:NLS-GFP”. Instead, the reporter line in Col-0 was obtained from Pfeiffer et al. (2016) and carries a pWUS::3xVenus-NLS transgene conferring BASTA resistance. During the introduction of this reporter into the cle40-2 background, no BASTA selection was applied, the resulting F3 generation was not stable and the pWUS::3xVenus-NLS transgene segregated. Therefore, our observation that cle40-2 shows reduced pWUS::3xVenus-NLS activity is not based on the analysis of homozygous transgenic plants and we can no longer support this statement.
Consequently, as a precautionary measure, we removed Figure 7, including Figure 7—figure supplement 1 and Figure 7—figure supplement 2 as well as all statements based on these data. The new Figure 7 was previously included as Figure 7—figure supplement 3. Accordingly, we also provide an adjusted model (new Figure 8) for CLE40 function in the inflorescence meristem.
Corrected Figure 8 (changes to legend text underlined):
Schematic model of two intertwined signalling pathways in the shoot meristem.
(A, B) Schematic representation of two intertwined signalling pathways in the inflorescence meristem (IFM) of Arabidopsis thaliana. CLV3 in the central zone (CZ) binds to the LRR receptor CLV1 to activate a downstream signalling cascade which leads to the repression of the transcription factor WUS. In a negative feedback loop WUS protein moves to the stem cells to activate CLV3 gene expression. In the peripheral zone (PZ) of the IFM, a second signalling pathway controls meristem growth by CLE40 and its receptor BAM1. CLE40 binds to BAM1 in an autocri…
Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.
The American College of Obstetricians & Gynecologists (ACOG) released a maternal immunization schedule for 2026, the first time the organization has issued formal vaccine guidance that does not align with federal recommendations.
Delirium after surgery may be a strong predictor of long-term cognitive decline in older adults independent of illness or frailty, a recent study suggests.
Approximately 19% of US adolescents and young adults reported using an artificial intelligence (AI) chatbot for mental health advice in 2025, according to a study published in JAMA Pediatrics.