HIV-1 entry into susceptible cells requires the dynamic interaction of its envelope (Env) glycoprotein with the host cell receptor CD4 and a co-receptor, either CCR5 or CXCR4. While the core molecular mechanisms driving Env-receptor interactions and subsequent membrane fusion are well characterized, the precise nanoscale spatial reorganization of these co-receptors at the viral binding site remains poorly defined. In this study, we employed single-particle tracking total internal reflection fluorescence (SPT-TIRF) microscopy to quantitatively analyze nanoscale organizational changes of CXCR4 on the surface of human CD4<sup>+</sup> T cells following binding by X4-tropic HIV-1. Our data reveal that both recombinant X4-gp120 and virus-like particles expressing physiological levels of X4 Env proteins (gp120 and gp41) promote CXCR4 clustering, a phenomenon linked to cell infection. Furthermore, these ligands induced oligomerization of CXCR4<sup>R334X</sup>, a naturally occurring mutant associated with WHIM syndrome that supports HIV-1 infection, but fails to oligomerize in response to CXCL12. Our findings establish a link between CXCR4 clustering and HIV-1 infection, enhancing our understanding of the initial events in viral attachment and entry. These results further suggest that HIV-1 depends on a specific spatial arrangement of co-receptors, distinct from that induced by their natural chemokine ligands, highlighting the critical role of cell-surface receptor spatial organization in dictating cellular function.
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Individuals, even with matched genetics and environment, show substantial phenotypic variability. This variability may be part of a bet-hedging strategy, where populations express a range of phenotypes to ensure survival in unpredictable environments. In addition, phenotypic variability between individuals (‘bet-hedging’), individuals also show variability in their phenotype across time, even absent external cues. There are few evolutionary theories that explain random shifts in phenotype across an animal's life, which we term drift in individual phenotype. We use individuality in locomotor handedness in <i>Drosophila melanogaster</i> to characterize both bet-hedging and drift. We use a continuous circling assay to show that handedness spontaneously changes over timescales ranging from seconds to the lifespan of a fly. We compare the amount of drift and bet-hedging across a number of different fly strains and show independent strain-specific differences in bet-hedging and drift. We show manipulation of serotonin changes the rate of drift, indicating a potential circuit substrate controlling drift. We then develop a theoretical framework for assessing the adaptive value of drift, demonstrating that drift may be adaptive for populations subject to selection pressures that fluctuate on timescales similar to the lifespan of an animal. We apply our model to real-world environmental signals and find patterns of fluctuations that favor random drift in behavioral phenotype, suggesting that drift may be adaptive under some real-world conditions. These results demonstrate that drift plays a role in driving variability in a population and may serve an adaptive role distinct from population-level bet-hedging.
Respiration is governed by a widespread network of cortical and subcortical structures. This complex communication between the brain and lungs is altered in pathological conditions. Apnoea – the cessation of respiration – is a common condition in infants, particularly those born prematurely. Apnoea in infants is believed to relate to immaturity of brainstem respiratory centres; involvement of the cortex in respiration in infants has yet to be explored. We investigated if there was any evidence for cortical coupling with respiration in newborn humans and whether it relates to apnoea. Using simultaneous electroencephalography (EEG) and impedance pneumography, we investigated interactions between cortical and respiratory activity (known as cortico-respiratory coupling) using phase-amplitude coupling. We show that cortico-respiratory coupling is present in premature and term newborns (104 recordings from 68 infants; 34.5±2.6 weeks postmenstrual age), identifying an interplay between breathing phase and EEG amplitude. We further shed light on the biological meaning by revealing that the strongest coupling occurs during inspiration and that cortical activity precedes respiration, with coupling strongest over frontocentral regions. Whilst our study was limited in spatial resolution, and determining causality is challenging, we believe these findings support the notion that the cortico-respiratory coupling observed here constitutes communication between cortical motor areas and lung effectors. Moreover, we show that cortico-respiratory coupling is negatively correlated with the rate of apnoea, revealing novel insight into this common and potentially life-threatening neonatal pathology.
In Reply We thank Dr Liu and colleagues for their thoughtful engagement with our study and for highlighting important methodological considerations. We welcome the opportunity to clarify these points.
In the Research Letter titled “Trends in Vitamin K Administration Among Infants,” published in the December 8, 2025, issue of JAMA, there were errors in the reported total number of newborns included in the study. It should have been noted that 15 354 of 526 341 newborns in 2017 and 37 187 of 717 402 newborns in 2024 did not receive intramuscular vitamin K. This article was corrected online.
This descriptive analysis uses a subset of data from the Malarial Impact on Neurobehavioral Development (MIND) cohort study to assess whether severe malaria in Ugandan children is associated with long-term cognitive impairment or decreased academic achievement.
This review discusses the epidemiology, clinical presentation, diagnosis, surgical management, histopathologic and molecular characteristics, and adjuvant treatment for endometrial cancer.
Head-mounted miniscopes have enabled functional fluorescence imaging in freely moving animals. However, current technology is limited to recording at most two spectrally distinct fluorophores, severely restricting the number of identifiable cell types. Here, we introduce multiplexed neuronal imaging (Neuroplex), a pipeline combining miniscope Ca<sup>2+</sup> recordings with in vivo multiplexed confocal spectral imaging to distinguish nine projection-defined neuronal subtypes through the same GRIN lens. By co-registering defined neurons with fluorophore-specific spectral fingerprints via linear unmixing, we link projection-defined identities to behaviorally relevant neuronal activity. This approach overcomes spectral constraints of miniscopes, enabling circuit-level dissection of behavior in single animals.
Mating in insects typically triggers a post-mating response (PMR) in females, characterized by reduced receptivity to re-mating and increased oviposition, which ensures numerous and viable offspring and male paternity. This PMR is induced by male seminal factors, such as sex peptide in <i>Drosophila melanogaster</i>, as well as intrinsic female signaling components. The latter signaling remains poorly understood in most insects, including the devastating rice pest, the brown planthopper (BPH) <i>Nilaparvata lugens</i>. Here, we show that the neuropeptide corazonin (CRZ) and its receptor (CrzR) are critical for the PMR in female BPHs. Peptide injection, RNAi knockdown, and CRISPR/Cas9 mutagenesis confirm that intact CRZ signaling reduces re-mating frequency and increases ovulation in mated BPH females. The CrzR is highly expressed in the female reproductive tract, and CrzR knockdown phenocopies CRZ diminishment. Importantly, female CRZ/CrzR signaling is required for male seminal factors, such as the peptide maccessin, to induce the PMR; with disrupted <i>CrzR</i> signaling, injection of seminal fluid or maccessin fails to reduce female receptivity. Notably, CRZ is not produced in male accessory glands (MAGs) of BPHs and thus not transferred during copulation. We furthermore demonstrate that also in <i>D. melanogaster</i> disrupted CRZ signaling increases female re-mating and reduces oviposition, while CRZ injection suppresses virgin receptivity and increases oviposition. Finally, we detected no CRZ in the MAG of <i>D. melanogaster,</i> supporting its role as an endogenous signal in the female PMR also in this species. In summary, our findings reveal a conserved role of endogenous CRZ signaling in regulating the female PMR and demonstrate that female CRZ signaling and male-derived signals cooperate to induce post-mating transitions in BPHs and <i>D. melanogaster</i>. CRZ is a paralog of the peptide gonadotropin-releasing hormone, known to regulate reproduction in v…
Politicians are reducing public funding for science and dismantling scientific institutions for ideological reasons in Argentina and the United States. It appeared as if something similar could happen in the Netherlands, but the collapse of a coalition government led to a reprieve. How should the scientific community respond to such crises?
In Reply We appreciate that a one-size-fits-all approach to breast cancer screening is increasingly anachronistic, given the heterogeneity of breast cancer and the imbalanced distribution of risk factors across the population. The WISDOM results demonstrated that a risk-based strategy can stratify population risk, facilitating personalized screening and prevention strategies while preserving safety.
This JAMA Clinical Guidelines Synopsis summarizes the American College of Gastroenterology’s 2024 guideline on treatment of Helicobacter pylori infection.
This Medical News article discusses the emergence of a new, research-focused independent autism group in the US following recent changes to the federal Interagency Autism Coordinating Committee.
In this narrative medicine essay, a palliative care physician discusses the impact that the death of her brother had on her time as an attending physician working in the emergency department.
This Viewpoint explores the entry of AI into clinical care, the role of the US Food and Drug Administration, and the associated legal, public health, and medical implications.
Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.
The US Food and Drug Administration (FDA) approved insulin icodec-abae, marketed as Awiqli, making it the first once-weekly basal insulin treatment option for adults with type 2 diabetes.
The US Food and Drug Administration (FDA) approved the oral glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron, marketed as Foundayo, for daily use in people with overweight or obesity. Unlike other oral GLP-1 drugs, orforglipron can be taken any time of day without food or water restrictions.
The burden of hypertension has increased globally over the past 2 decades, particularly in low- and middle-income countries, according to a study published in the Journal of the American College of Cardiology.
Promotion of prescription drugs by social media influencers was consistently associated with misinformation, research found.
This JAMA Medical News article discusses the unusual trajectory of BA.3.2, the most recent version of SARS-CoV-2 to be designated a Variant Under Monitoring by the World Health Organization.
The World Health Organization (WHO) released new guidelines on tests for tuberculosis, encouraging the use of portable diagnostics, pooling of sputum samples, and tongue swabs.
In 1948, Salil Ghosh wrote of the near-miraculous recovery of several children with severe “malignant malaria” who had been treated with quinine. One illustrative patient, a “girl aged 9 years,” was admitted with 2 days of “unconsciousness with delirium” and found to have “rings plenty,” the classic finding of blood-stage Plasmodium falciparum infection seen on peripheral blood smear. Following administration of intramuscular, and then oral, quinine, the patient “went home in perfect health.”
Some children with obesity may not have symptoms such as high blood pressure or elevated triglycerides. But recent findings suggest that even if children with obesity appear metabolically healthy, they may still benefit from treatment.