Browse Articles

Auditory feedback effect on temporal patterns during self-pacing treadmill walking

Self-pacing treadmills provide advantages for assessing locomotion such as having a controlled environment and ability to accurately collect prolonged data, but the variable sounds from the treadmill belt motors when changing speed could provide artificial sensory feedback to walkers that may influence their gait while on the self-pacing treadmill. We hypothesized that temporal measures of gait on a proportionally-controlled self-pacing treadmill would be significantly different between when sound is present vs removed. Participants (n = 31) walked under two different conditions for five-minute periods each on the self-pacing treadmill: one without headphones, and the other with noise-cancelling headphones playing brown noise to mask the treadmill motor sounds. Mixed effects models were used to assess the impact of condition on temporal gait patterns. A custom accelerometer-based algorithm was created to detect gait events while on the treadmill. Significant differences were found in the average values of swing time, step time, and gait speed between the treadmill conditions. These differences between the two treadmill conditions suggest that self-pacing treadmill walkers may utilize the variable belt motor sounds available to them. Given the potential incorporation of auditory feedback for motor planning when walking on the self-pacing treadmill, researchers should consider belt motor sounds as a potential factor that affects gait patterns.

Quantitative MRI of the hippocampus reveals microstructural trajectories of aging and Alzheimer’s disease pathology

Hippocampal degeneration is a feature of both normal aging and Alzheimer’s disease (AD). Prior to macroscopic degeneration, microstructural changes occur such as demyelination, iron deposition, or subtle atrophy, which can be characterized in vivo using MRI. We topographically mapped measures of microstructure and macrostructure across the unfolded surface of the hippocampus in 224 healthy older adults at risk for AD (aged 57 to 87) and 37 younger adults (aged 18 to 37). We describe three spatial regions of unique structural covariance between four parameters sensitive to microstructural tissue properties (R1, MTsat, R2*, PD) and macrostructure (surface thickness), with high convergence with previous spatial segmentations. We demonstrate both cross-sectional and longitudinal associations of microstructure with healthy aging across the lifespan, AD pathological hallmarks, genetic risk, and cognition. These associations had subtle variations across different spatial areas of the hippocampus. We report associations between age and qMRI measures sensitive to macromolecular concentration (R1, MTsat) and paramagnetic susceptibility (R2*), consistent with mechanisms of demyelination and increased iron deposition as key hallmarks of the aging hippocampus and in presymptomatic stages of AD. qMRI measures did not explain more variance in delayed recall than global PET measures, suggesting variation in cognitive performance in aging and incipient AD is influenced by factors beyond hippocampal microstructure. We demonstrate the utility of quantitative MRI to provide greater insight into hippocampal health compared to typical macrostructural measures through “in vivo histology,” opening a window to understanding neuropathological mechanisms in the earliest stages of age- and disease-related neurodegeneration.

Antibacterial and antiviral potential of harmalacidine hydrochloride, a β-carboline alkaloid, against respiratory tract pathogens: Staphylococcus aureus and H1N1 influenza virus

Respiratory infections remain a leading cause of morbidity and mortality, necessitating new therapeutic strategies. This study evaluated the antiviral and antibacterial activities of harmine, harmaline, and harmalacidine hydrochloride against H1N1 influenza virus and Staphylococcus aureus , key respiratory pathogens. The in vitro antiviral activity of the tested compounds against the H1N1 virus was evaluated using a plaque assay. Harmalacidine hydrochloride demonstrated notable activity, with an IC 50 of 68.2 ± 0.8 µg/mL, while harmine and harmaline showed no significant effects at non-cytotoxic concentrations. The potential antibacterial action of the tested compounds was initially investigated by agar well diffusion method, which revealed clear zones of inhibition around the wells. Subsequently, their minimum inhibitory concentrations (MICs) were recorded using the broth microdilution method. Harmalacidine hydrochloride exhibited the highest antibacterial action with MICs from 16 to 128 µg/mL. Based on these findings, further investigations were conducted to assess the effect of harmalacidine hydrochloride on membrane integrity and permeability, cellular morphology, and biofilm formation. A noticeable reduction ( p  < 0.05) in the membrane integrity and a distinct escalation ( p  < 0.05) in the permeability were noticed in 46.15% and 53.85% of the tested isolates, respectively. Moreover, scanning electron microscopy revealed pronounced distortion in cellular morphology following harmalacidine hydrochloride treatment. The compound also exhibited antibiofilm activity, as demonstrated by the crystal violet assay, alongside a downregulation of biofilm-associated gene expression. Molecular docking revealed that harmalacidinium ion binds strongly to the Accessory Gene Regulator A ( AgrA ) of S. aureus , suggesting antibacterial activity through inhibition of quorum sensing-mediated virulence. It also showed high affinity for H1N1 neuraminidase and polymerase basic protein 2 (PB2), indicating potential antiviral activity. However, experimental enzyme assays and in vivo studies are required to confirm the proposed antiviral and antibacterial mechanisms.

Mineralized sclerites in the gorgonian coral <i>Leptogorgia chilensis</i> as a natural jamming system

The soft corals (Cnidaria, Octocorallia), a diverse group of colonial marine invertebrates, can reversibly tune their body stiffness in response to external stimuli. This capability is attributed to their dynamic skeletal systems, which consist of thousands of mineralized skeletal elements, called sclerites, embedded within a gel-like matrix that swells/deswells and unjams/jams the sclerites, thus modulating skeletal stiffness. While sclerite morphology is widely used for species identification, its role in the mechanical performance of a soft coral’s skeletal system is largely unknown. Here, we investigated structure-jamming relationships in sclerite-based skeletal architectures using the red gorgonian octocoral Leptogorgia chilensis as a model system. The sclerites of L. chilensis exhibit a shaft-like geometry with two axial branches and two sets of triradiate side branches, which are aligned with the crystallographic symmetry of the constituent magnesium-containing calcite. By combining multiscale three-dimensional (3D) structural characterization, parametric geometrical modeling, 3D printing, mechanical testing, and discrete element simulations, we demonstrate how sclerite geometry achieves a balanced jamming performance in terms of stiffness, weight, strength, and fracture resistance in comparison to alternative geometries parametrically modified from the native sclerites (e.g., changes in the length and number of side branches). We also found that these performance metrics are achieved through the effective interlocking among side and axial branches, which is further enhanced by the fractal-like microscopic spikes on the branch tips. The findings in this natural jamming system offer insights for designing synthetic mechanotunable material architectures for a wide range of applications, from soft robotics to mechanical dampeners.

What do the differences and commonalities in doctoral dissertation acknowledgments across disciplines reveal?

Acknowledgments in academic dissertations occupy a unique role within scholarly communication. Prior research has investigated acknowledgments through lenses such as funding attribution, genre analysis, and linguistic features. This study examines acknowledgments in doctoral dissertations from Chinese universities, organized by broad disciplinary categories. Utilizing BERTopic modeling, the research identifies topic keywords embedded within dissertation acknowledgments. Furthermore, computational linguistics techniques are employed to quantitatively evaluate the content and stylistic attributes of these acknowledgments, complemented by hierarchical clustering analysis to explore cross-disciplinary similarities. The topic modeling results indicate that acknowledgments by Chinese doctoral students frequently convey emotional reflections and exhibit distinct disciplinary traits. Additionally, hierarchical clustering shows that disciplines with similar characteristics exhibit greater similarity in the content and writing style of their acknowledgments, indicating that academic training influences researchers’ writing to some degree. This study seeks to catalyze further scholarly inquiry into this domain, advocating for expanded investigations from perspectives including psychology, neuroscience, and cross-cultural studies.

FibrilPaint to determine the length of Tau amyloids in fluids

Tau aggregation into amyloid fibrils is linked to the development of neurodegenerative diseases, including Alzheimer’s disease (AD). The molecular processes driving aggregation in disease are still being uncovered, highlighting the need for innovative tools to study aggregation reactions. Here, we introduce FibrilPaint1 as a tool to measure the size of Tau amyloid fibrils in fluids, from early aggregation stages to mature fibrils. FibrilPaint1 is a 22mer peptide with exciting properties: i) FibrilPaint1 binds fibrils with nanomolar affinity; ii) it also binds to precursors, down to a size of only 4 layers; iii) it does not bind to monomers; iv) it is fluorescently labeled, which allows monitoring and localizing interactions; v) FibrilPaint1 recognizes various Tau fibrils, including patient-derived fibrils from AD, corticobasal degeneration (CBD), and frontotemporal dementia (FTD); vi) it also binds to fibrils from amyloids derived from Amyloid-β, α-synuclein, and huntingtin vii) FibrilPaint1 is selective for the amyloid state and does not have background binding to amorphous aggregates, blood serum, or cell lysate. In combination with flow-induced dispersion analysis (FIDA), a microfluidics technology, we determined the molecular size of amyloid fibrils with submicroliter sample volumes. This setup acts as a molecular ruler at layer resolution—we determined Tau fibril length from 4 to 1100 layers in solution. This is an interesting parameter for molecular studies in dementia, with potential for diagnostic applications.

Keeping Wnt in check for efficient checkpoint blockade in glioblastoma

Global impact of anthropogenic NH ₃ emissions on upper tropospheric aerosol formation

Anthropogenic ammonia (NH 3 ) emissions have significantly increased in recent decades due to enhanced agricultural activities, contributing to global air pollution. While the effects of NH 3 on surface air quality are well documented, its influence on particle dynamics in the upper troposphere-lower stratosphere (UTLS) and related aerosol impacts remain unquantified. NH 3 reaches the UTLS through convective transport and can enhance new particle formation (NPF). This modeling study evaluates the global impact of anthropogenic NH 3 on UTLS particle formation and quantifies its effects on aerosol loading and cloud condensation nuclei (CCN) abundance. We use the EMAC Earth system model, incorporating multicomponent NPF parameterizations from the CERN CLOUD experiment. Our simulations reveal that convective transport increases NH 3 -driven NPF in the UTLS by one to three orders of magnitude compared to a baseline scenario without anthropogenic NH 3 , causing a doubling of aerosol numbers over high-emission regions. These aerosol changes induce a 2.5-fold increase in upper tropospheric CCN concentrations. Anthropogenic NH 3 emissions increase the relative contribution of water-soluble inorganic ions to the UTLS aerosol optical depth (AOD) by 20% and increase total column AOD by up to 80%. In simulations without anthropogenic NH 3 , UTLS aerosol composition is dominated by sulfate and organic species, with a marked reduction in ammonium nitrate and aerosol water content. This results in a decline of aerosol mass concentration by up to 50%. These findings underscore the profound global influence of anthropogenic NH 3 emissions on UTLS particle formation, AOD, and CCN production, with important implications for cloud formation and climate.

Shared cognitive biases influence numerical judgments in macaques and crows

Cognitive biases, which come from the shortcuts our brains use to make decisions, often lead people to misjudge sizes, amounts, or other magnitudes. However, it is still unclear how these biases evolved. Nonhuman animals like primates and corvids share with humans a nonsymbolic number sense. Whether biases in magnitude estimation are evolutionarily widespread in animals remains an open question. We investigated numerical estimation in macaque monkeys and carrion crows—two distantly related but numerically proficient vertebrates—using a delayed match-to-numerosity task with dot arrays. Both species exhibited key biases commonly observed in humans during numerical estimation tasks: scalar variability (increasing response variability with numerosity), regression to the mean (overestimation of small and underestimation of large numerosities), and a sequential effect (estimates biased toward previous trial numerosities). Traditionally, these biases have been attributed either to static influences of overall task history or to dynamic effects from recent trials. Here, we demonstrate that a Bayesian model incorporating dynamic priors based on multiple previously encountered numerosities can account for all observed behavioral patterns. Our findings suggest that numerical judgments in both species are shaped by uncertainty and the integration of recent experience, revealing shared Bayesian-like mechanisms for cognitive biases across distantly related animals.

Regional postdeforestation weathering feedback drove diachronous C–S cycle perturbations during the end-Permian crisis

The Permian–Triassic (P-Tr) transition (~252 Ma) witnessed Earth’s most severe biocrisis, which has long been linked to Siberian Traps volcanism and associated environmental upheaval. Major perturbation of the global carbon (C) and sulfur (S) cycles is mainly inferred from marine δ 13 C and δ 34 S records, whereas few existing terrestrial records link δ 34 S fluctuations to widespread dispersal and fallout of volcanogenic sulfate aerosols. Mounting evidence, however, reveals that the collapse of P-Tr terrestrial ecosystems was diachronous, questioning a hypothesized globally synchronous common forcing. Here, we present records of pyritic multiple-S isotopes (δ 34 S py and Δ 33 S) and bulk organic δ 13 C for a paleotropical peatland drill core (HK-1) from Southwest China. The δ 34 S py variations define three distinct phases with a notable decline in δ 34 S py across the P-Tr transition, suggesting substantially elevated terrestrial sulfate influx coincident with major carbon cycle perturbation. Notably, overall small positive Δ 33 S values (+0.01 to +0.12‰) rule out a dominant role for stratospheric sulfates. Collectively, the observed changes in δ 13 C org , δ 34 S py , and Δ 33 S support catastrophic collapse of the Cathaysian Flora leading to intensified weathering and sulfate release. This inferred event, slightly after the P-Tr marine extinction, postdates by several 100-ky terrestrial floral collapse and perturbation of the C–S cycles documented in the high-latitude Sydney Basin. Cross-latitudinal diachroneity of terrestrial ecosystem collapse and consequent C–S perturbation challenges the hypothesis of a single, global volcanic driver. Rather, regional deforestation and its cascading effects overprinted on the global perturbations of biogeochemical cycles emerge here as critical factors shaping Earth’s largest recorded crisis.

The war of the worldviews

Inflammasome targeting for periodontitis prevention is sex dependent

Inflammasome initiates inflammation via the maturation of interleukin-1 beta (IL-1β). Periodontitis is a prevalent, male-biased disease characterized by inflammation-driven bone loss, yet the mechanism(s) of this sex bias is unknown. This study explored whether enhanced inflammasome represents a causal mechanism for this bias. Analyses of three separate human studies (&gt;6,200 samples) show that males have significantly higher IL-1β in the gingival crevicular fluid than females during health and periodontitis. This pattern is experimentally reproduced with different versions of the ligature-induced periodontitis mouse model where males show greater IL-1β secretion than females. The inflammasome drives bone resorption in males but not females as revealed by analyses of inflammasome gene-deletion mice. Pharmacologic treatment with a caspase-1/4 inhibitor reduces inflammatory cell infiltration, dampens osteoclastogenesis signaling (via the receptor activator of nuclear factor-kappa B pathway), and prevents bone resorption in males but not females during experimental periodontitis. While ovariectomized females show no change in their nonresponsiveness to caspase-1/4 inhibition, orchiectomized males no longer respond to the inhibition, suggesting the importance of an intact male reproductive system in the mediation of this inhibition. Thus, our study identifies inflammasome activation as causal for male-biased experimental periodontitis and supports sex-stratified studies to foster future advancement of inflammasome therapeutics in periodontics.

Decreased hippocampal neurite density in late-middle-aged adults following prenatal exposure to higher levels of maternal inflammation

In animal models, exposure to heightened maternal inflammation in utero is associated with altered offspring hippocampal development, including reduced dendritic arborization and density. However, the effects of prenatal maternal inflammation (PNMI) on offspring hippocampal microstructure in humans remain unclear. Here, we examined the relationship between exposure to PNMI and neurite density in the hippocampus and its subfields among offspring during late middle age. Participants included 72 mother–offspring dyads from the Child Health and Development Studies (CHDS) cohort. Data for four inflammatory biomarkers (IL-6, IL-8, IL-1 receptor antagonist [IL-1RA], and soluble Tumor Necrosis Factor (TNF) receptor-II) were available from first- and second-trimester maternal sera. Neurite density in the offspring hippocampus and its subfields was estimated using microstructural modeling of offspring’s diffusion-weighted MRI data (mean age of offspring at imaging = 59 y; 51% male). We estimated the relationship between each biomarker and region-of-interest’s neurite density. Higher first-trimester maternal IL-1RA and IL-6 levels were associated with lower offspring hippocampal neurite density. These relationships were specific to the Cornu Ammonis 3, Cornu Ammonis 4, dentate gyrus, and subiculum subfields. In addition, higher second-trimester IL-6 was associated with lower subiculum neurite density. Our findings reveal that exposure to heightened prenatal levels of maternal inflammation is linked to altered offspring hippocampal microstructure in late middle age, which could have implications for memory decreases during this period and may be relevant for understanding the risk of aging-related cognitive changes.

Confronting the inevitable: Harnessing technology to contain systemic scientific fraud

Gain of Alternative Allele Expression of LINC02449 at rs149707223 in Schizophrenia and Bipolar Disorder: Inducing Synaptic Transmission and Behavioral Deficits in Mice

Abstract Bipolar disorder (BD) and schizophrenia (SZ) are complex psychiatric disorders with overlapping features. Their heterogeneity may arise from interactions between genetic variants and environmental or epigenetic modifiers. Allele-specific expression (ASE), an imbalance in expression between gene alleles, provides a key mechanism linking these interactions to disease. We conducted transcriptomic and genomic analyses in phenotype-discordant monozygotic twins to investigate ASE in psychiatric risk. Nine ASE-affected long non-coding RNAs were identified, including LINC02449 , which showed a consistent allele-specific shift in BD/SZ patients favoring the alternative G allele at rs149707223. Functional analyses revealed that overexpression of the LINC02449 G allele in mice induced social deficits and repetitive behaviors. These phenotypes were associated with enhanced excitatory transmission within the mPFC-NAc circuit, mediated by the synaptic regulator CPLX1. Our findings demonstrate that ASE-driven dysregulation of LINC02449 contributes to synaptic and behavioral abnormalities, underscoring ASE as a potentially important regulatory mechanism in BD and SZ pathogenesis.

Science and sensitivity in the study of not having sex

Pyrogenic carbon contribution to tropical savanna soil carbon storage

Abstract Savannas are fire-prone ecosystems that contribute substantially to global fire emissions, but these emissions may be partly offset by deposition of fire-derived, persistent pyrogenic carbon (PyC) in soils. Although estimates of PyC contributions to soil organic carbon (SOC) storage in savanna exist, factors driving its accumulation remain unclear due to limited measurements with consistent methods. To address this, we sampled 253 sites across tropical savannas in Kruger National Park, South Africa, spanning broad gradients in fire regimes, grass biomass, rainfall, and soil texture. Here we show, PyC measured with H 2 O 2 /HNO 3 digestion contributed, on average, 14.08% (se = 0.36%, n  = 253) of SOC in surface soils, with values up to 40%. While fire frequency and grass biomass influenced soil PyC stocks, savannas with higher clay content and lower rainfall – conditions favoring PyC preservation – tended to accumulate more. These results demonstrate PyC’s significant contribution to SOC storage and highlight environmental factors driving its accumulation in tropical savannas, providing an empirical basis for understanding fire’s role in the savanna carbon cycle.

Discarded cigarette butts as overlooked reservoirs and amplifiers of antibiotic resistance genes and pathogens in urban green spaces

Cigarette butts are widely discarded in urban green spaces, yet their microbial health risks remain poorly understood. In a nationwide survey across China, we investigated the presence, sources, health risks, and drivers of antibiotic resistance genes (ARGs) and potential pathogens in discarded cigarette butts. Shotgun metagenomic and full-length 16S ribosomal rRNA (rRNA) sequencing revealed that cigarette butts harbored significantly higher abundances of ARGs and bacterial pathogens than plant litter or soil. Health risk assessment further showed that cigarette butts carried ARGs with greater mobility, clinical relevance, and pathogenic potential. Genomic analyses highlighted enrichment of ARG-carrying pathogens, particularly Enterobacteriaceae and Pseudomonas , with mobile genetic elements and oxidative stress responses as key contributors. Functional assays, including plasmid transfer, transcriptomic profiling, and single-cell Raman spectroscopy, demonstrated that cigarette butts promoted horizontal gene transfer and upregulated key ARGs (e.g., mexE , mexF , cfrC ) under stress conditions. Scanning electron microscopy confirmed biofilm formation on cigarette fibers, supporting enhanced bacterial persistence. Source-tracking analyses identified both human oral and environmental sources of the enriched ARGs and pathogens in cigarette butts. Finally, socioeconomic factors such as lower gross domestic product (GDP), reduced education, and poor sanitation were strongly associated with elevated ARG and pathogen risks. Collectively, our findings identify cigarette butts as overlooked yet potent vectors of ARG and pathogen dissemination in urban green spaces, underscoring the need for targeted interventions within a One Health framework.

Amygdala AVPR1A mediates susceptibility to chronic social isolation in female mice

Optimizing multifunctional fluorescent ligands for intracellular labeling

Enzyme-based self-labeling tags enable the covalent attachment of synthetic molecules to proteins inside living cells. A frontier of this field is designing cell-permeable multifunctional ligands that contain fluorophores in combination with affinity tags or pharmacological agents. This is challenging since attachment of additional chemical moieties onto fluorescent ligands can adversely affect membrane permeability. To address this problem, we examined the chemical properties of rhodamine-based self-labeling tag ligands through the lens of medicinal chemistry. We found that the lactone–zwitterion equilibrium constant ( K L–Z ) of rhodamines inversely correlates with their distribution coefficients (log D 7.4 ), suggesting that ligands based on dyes exhibiting low K L–Z and high log D 7.4 values, such as Si-rhodamines, would efficiently enter cells. We designed cell-permeable multifunctional HaloTag ligands with a biotin moiety to purify mitochondria or a JQ1 appendage to translocate BRD4 within the nucleus. We found that translocation of BRD4 to constitutive heterochromatin in cells leads to apparent increases in transcriptional activity. These fluorescent reagents enable affinity capture and translocation of intracellular proteins in living cells, and our general design concepts will facilitate the design of multifunctional chemical tools for biology.