Browse Articles

Daily briefing: Youthifying 'mirror' brings back more vivid childhood memories

Optical properties, surface roughness, and bacterial adhesion of feldspathic CAD/CAM ceramic material after immersion in staining media with different pH

Low-density lipoprotein cholesterol and risk of COPD: a Mendelian randomization study

Abstract Statins have shown effects on exacerbation rates and lung function in individuals with chronic obstructive pulmonary disease (COPD) in randomized controlled trials. This has led to speculation that elevated LDL cholesterol may increase the risk of adverse COPD outcomes. We tested the hypothesis that high LDL cholesterol is causally associated with increased risk of severe COPD exacerbation, COPD-specific mortality, and spirometric COPD through a one-sample Mendelian randomization study design using individual-level data in two cohorts. We examined 108,438 adults from the Copenhagen General Population Study (CGPS). A weighted allele score was calculated using nine biologically relevant genetic variants associated with LDL cholesterol levels, and causal risk estimates for the three outcomes were determined using instrumental variable analysis. Findings were validated using one-sample Mendelian randomization in 389,627 individuals from the UK Biobank (UKB). Causal odds ratios from the CGPS were not statistically significant for severe COPD exacerbation (odds ratio (OR) 1.12 (95% CI: 0.88–1.42), p  = 0.34) or COPD-specific mortality (OR 1.08 (0.69–1.69), p  = 0.74). Similar findings were seen in the UKB. Causal estimates showed a decreased risk of cross-sectional spirometric COPD with 1 mmol/L (39 mg/dL) higher LDL cholesterol in the CGPS (OR 0.78 (0.66–0.92), p  < 0.001); however, causal estimates were not statistically significant in the UKB (OR 1.03 (0.95–1.11), p  = 0.50). Sensitivity analyses using MR Egger, inverse-variance weighted, weighted median, and weighted mode methods did not indicate a true causal association for any outcome in either cohort. In conclusion, in the CGPS and UKB, high LDL cholesterol did not causally increase the risk of severe COPD exacerbation and COPD-specific mortality. Further, our findings do not provide consistent evidence to support a causal role of high LDL cholesterol in reducing the risk of developing COPD.

Bioactive pigment production by marine bacteria from Colombian estuarine and deep–sea environments

Giant cancer study reveals effectiveness of ‘off label’ treatments

FT-MDNNMDs: early detection of breast cancer using fine-tuned multi-deep neural networks with TCGA and clinical image datasets

Abstract Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Early and accurate detection is critical for improving survival rates and enabling effective treatment. This research proposes a fine-tuned Multi-Deep Neural Network model with Multiple Datasets (FT-MDNNMDs). The proposed system employs a hierarchical classification strategy, first distinguishing cancer from normal cases, and subsequently classifying cancer-positive cases into Stage II and Stage III categories. The model integrates data from The Cancer Genome Atlas (TCGA) and a private clinical image dataset collected from hospitals in Pakistan. Preprocessing techniques, including image normalization, filtering, and Principal Component Analysis (PCA), are applied to enhance feature quality and reduce redundancy. Transfer learning and fine-tuning strategies are incorporated to further improve classification performance. The proposed model effectively distinguishes between benign and malignant tumors and accurately identifies stage II and stage III cases. Experimental results demonstrate that the fine-tuned MDNNMDs model achieves an accuracy of 99.57%, outperforming conventional machine learning algorithms such as Support Vector Machine (94.46%), Decision Tree (93.54%), and Naïve Bayes (91.22%). The model also achieved superior MCC (99.46%), F-score (99.57%), and recall (99.63%). In addition to algorithmic comparison, the performance of the proposed model is compared with existing breast cancer detection models, and it is revealed that the proposed model provides more accurate results than existing ones, with 1.5% to 3.0% better accuracy.

AI models ‘subliminally’ transmit biases when training other systems

On topological co-index polynomials for predictive modeling of the physicochemical properties of antiviral drugs

HAAC Ligation-Enabled Hierarchical Assembly: Deciphering the Synergy of α-Hydroxyl Aldehydes and 2-Aminooxazoles

Brainwide blood volume reflects opposing neural populations

Abstract The supply of blood to brain tissue is thought to depend on the overall neural activity in that tissue 1–9 , and this dependence is thought to differ across brain regions 3,4,10–13 and across brain states 3,14–17 . However, studies supporting these views have measured neural activity as a bulk quantity and related it to blood supply following disparate events in different regions. Here we measure fluctuations in neuronal activity and blood volume across the mouse brain, and find that their relationship is consistent across brain states and brain regions but differs in two opposing brainwide neural populations. Functional ultrasound imaging (fUSI) revealed that whisking, a marker of arousal, is associated with brainwide fluctuations in blood volume. Simultaneous fUSI and Neuropixels recordings showed that neurons that increase activity with whisking have distinct haemodynamic response functions compared with those that decrease activity. Their summed contributions predicted blood volume across states. Brainwide Neuropixels recordings revealed that these opposing populations coexist in the entire brain. Their differing contributions to blood volume largely explain the apparent differences in blood volume fluctuations across regions. The mouse brain thus contains two neural populations with opposite relations to brain state and distinct relationships to blood supply, which together account for brainwide fluctuations in blood volume.

A Direct Auditory Subcortical Route to the Amygdala Associated with Fear in Humans

Rapid and efficient fear processing is essential for survival. In vision, this function is supported by a well-characterized subcortical pathway consisting of direct projections from the pulvinar of the thalamus to the amygdala in the human brain. In contrast, the existence of an analogous shortcut for fear in audition has been demonstrated in nonhuman animals but remains unconfirmed in humans. To address this question, we used probabilistic streamline tractography and fixel-based analysis on diffusion-weighted images from Human Connectome Project participants of either sex to reconstruct candidate auditory subcortical pathways and examine their associations with affective and auditory behavioral measures. Our findings revealed a robust white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body (MGB) of the thalamus. Remarkably, higher fiber density in this tract was associated with better hearing ability in noise and increased self-reported fearfulness, supporting its role in auditory and affective function. Conversely, a control analysis of the core thalamocortical pathway from ventral MGB to primary auditory cortex, representing the main route for auditory processing, was associated with auditory ability but not with affective measures. These findings provide previously unreported evidence for an auditory colliculo-geniculo-amygdala "low road" in humans, aligning with evolutionarily conserved pathways for fear described in nonhuman species.

Sleep-Like Slow Waves during Wakefulness Mediate Attention and Vigilance Difficulties in Adult Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is characterized by behavioral variability and heightened inattention associated with increased mind wandering (MW) and mind blanking (MB). Individuals with ADHD frequently experience sleep disorders and excessive daytime sleepiness, suggesting interactions between attention and arousal systems. Research examining brain activity using electroencephalography (EEG) has demonstrated that sleep-like slow waves (SWs) during wakefulness are linked to inattention in neurotypical individuals following sleep deprivation, yet their role in ADHD remains unclear. This study investigated whether individuals with ADHD present with altered waking SW distribution compared with neurotypical controls and whether SWs explain attentional difficulties in ADHD. Adults with ( n  = 32) and without ADHD ( n  = 31) completed a sustained attention task while EEG recorded brain activity. Mental state probes (on-task, MW, MB) were embedded within the task. Sleep-like SWs reflect cortical slowing and were detected from EEG activity. Omission/commission errors, reaction time (RT), RT variability, mental state reports, and subjective sleepiness were analyzed. Mediation analysis examined whether SW density explained ADHD-related performance differences. Individuals with ADHD exhibited more commission errors, MW and MB, more theta oscillations over frontotemporal electrodes, and higher SW density (SW/minute) over parietotemporal electrodes. Increased SW density correlated with higher omission errors, slower RTs, greater RT variability, and elevated sleepiness ratings. On-task reports were negatively correlated with SW density. Mediation analysis revealed that SW density significantly accounted for ADHD-related attentional difficulties. Wake SW may explain attentional difficulties in ADHD, providing a potential mechanistic link between sleep disturbances and attentional fluctuations.

Human Cerebral Blood Flow Activity with Diurnal Variation Differentially Correlated with the Suprachiasmatic Nucleus

The human circadian rhythm is controlled by central and peripheral clocks, primarily by the central clock in the suprachiasmatic nucleus (SCN). We investigated the diurnal variation of basic metabolism in the human cerebrum by measuring human baseline cerebral activity at rest contrasted with the SCN baseline activity. To this end, we utilized magnetic resonance imaging perfusion data of cerebral blood flow (CBF; N  = 27, including both sexes), where each participant was scanned four times a day at 6 h intervals (18:00, 24:00, 6:00, and 12:00 local time). Similarly to the SCN exhibiting higher CBF activity at noon, we observed a consistent temporal activity pattern in the brain regions, including the limbic (cingulate, insular, and temporopolar) and sensorimotor (visual and somatosensory/motor) areas. In contrast, the hippocampus showed higher activity at midnight and lower activity at noon. To examine the functional interaction between the SCN and the cerebral regions showing diurnal variation, we calculated the resting-state functional connectivity using the database of the Human Connectome Project ( N  = 164, including both sexes). Notably, the hippocampus demonstrated greater functional connectivity with the SCN than the other regions. These results suggest that cerebral regions exhibit differential patterns of diurnal variation associated with their functional connectivity with the SCN.

Suppression of In Vitro Epileptiform Activity by GABA Transaminase Inhibition Is Dependent on GABA _B Receptors and GABA Transporter Type 1 (GAT1)

Many antiepileptic drugs act by modulation of ionotropic GABA A receptors or effects on extracellular GABA concentrations. Metabotropic GABA B receptors also affect neuronal excitability but are not recognized as a target of antiepileptic drugs. We investigated effects of GABA B receptors and antiepileptic drug vigabatrin on epileptiform discharges induced by 4-aminopyridine (4AP) in hippocampal brain slices from male mice. The GABA B receptor agonist baclofen caused dose-dependent reduction in frequency of 4AP-induced epileptiform discharges but did not affect amplitude or duration of discharges. The inhibitory effects of baclofen were blocked by GABA B receptor antagonist CGP55845 (CGP) and the K + channel blocker Ba 2+ , indicating that baclofen was acting on GABA B receptors and activating GIRK channels. Baclofen effects were independent of GABA A receptors. Vigabatrin inhibits GABA transaminase, thereby increasing GABA concentrations. Pretreatment of brain slices with vigabatrin suppressed 4AP-induced discharges, significantly prolonging the latency to onset of spontaneous activity and reducing frequency of discharges. Similar to baclofen, vigabatrin effects on latency and frequency were reversed by GABA B antagonist CGP and the GIRK channel blocker Ba 2+ . Vigabatrin had no effect on 4AP-induced activity in GABA transporter type 1 knock-out mice (GAT1KO), suggesting that vigabatrin effects are dependent on GAT1 function. Our results indicate for the first time that a clinically used antiepileptic drug (vigabatrin) suppresses in vitro epileptiform activity via activation of GABA B receptors and GIRK channels. Data are consistent with a model that depicts altered thermodynamic equilibrium of GAT1 after GABA transaminase inhibition that leads to elevated extracellular GABA concentration and activation of GABA B receptors.

Unbalancing the Hydrogen Bond Accepting and Donating Effects of Water for Photoelectrocatalytic Ammonia Oxidation Reaction

Motoneurons Inhibitory Synapses Homeostatically Respond to Neuronal Activity and Modulate Amyotrophic Lateral Sclerosis Pathogenesis

Alterations in excitation/inhibition (E/I) balance and changes in motor neurons (MN) activity may contribute to MN vulnerability in ALS. The balance of pathogenic versus adaptive changes occurring in inhibitory synapses and affecting E/I balance remain unclear. Confocal microscopy of MN from P45 male SOD1G93A mice reveal downregulated GlyR but upregulated GABAR clusters at inhibitory synapses. GlyR and GABAR respond to PSAM and DREADD chemogenetic alterations of MN excitability, with increased activity driving increase in inhibitory clusters. An E3 ligase-conjugated intrabody (GFE3) degrades Gephyrin, decreases GABAR and GlyR clusters, increases net activity, and downregulates disease markers. However, simultaneous decrease of inhibition and increased activity by actPSAM and GFE3 shows no net beneficial effects on disease markers. Thus inhibitory synapses are involved in the early phases of ALS pathogenesis and respond to persistent homeostatic loops, and their suppression delivers a net activity increase, offering potential benefits on disease pathways.

Single-Cell-Resolution Fate Mapping Reveals Embryonic Venous Origins of Fenestrated Hindbrain Choroid Plexus Vasculature

In the brain, endothelial cell (EC) subtypes characterized by blood–brain barrier (BBB) properties or fenestrated pores form essential brain–blood interfaces and exhibit markedly distinct permeability. The choroid plexus (CP) establishes fenestrated vasculature lacking the BBB to efficiently regulate cerebrospinal fluid balance, yet its developmental origins and mechanisms remain poorly defined. Using single-cell-resolution fate mapping in zebrafish, we identify here two venous sources that give rise to the hindbrain myelencephalic CP (mCP) vasculature. RNAscope and BAC transgenic analyses reveal highly abundant and persistent expression of the venous marker flt4 in these EC lineages, supporting their identities. Unexpectedly, we find that these venous origins of the mCP vasculature also contribute ECs to diverse cranial vessels, including those that maintain low flt4 expression and later acquire BBB characteristics. Functionally, flt4 null and cytoplasmic-domain-deletion mutants exacerbate mCP vascularization defects when combined with vegfr2 signaling deficiency, without disrupting neighboring BBB-type vessels. Pharmacological data support this corequirement of Flt4 and Vegfr2 signaling in mCP vascularization and further suggest that the PI3K and ERK pathways are necessary for this process. Together, these findings reveal embryonic venous lineages and molecular pathways required for hindbrain CP vascularization and imply that Flt4 signaling contributes to the angiogenic separation of CP- and BBB-associated capillaries originating from shared embryonic domains.

GABA and Glx Distinctively Predict Motor Learning and Retention in Young and Older Adults

Gamma-aminobutyric acid (GABA) and glutamate are fundamental in neural plasticity. Motor learning is predicted by baseline levels of these metabolites and their modulation in the sensorimotor cortex (SM1), but less is known about the metabolic activity in other areas that support learning, such as the dorsolateral prefrontal cortex (DLPFC), as well as the practice-induced metabolic modulation and age-associated differences. We investigated whether: (1) motor learning induces a differential degree of metabolic modulation in the SM1 and DLPFC, (2) learning tasks with higher difficulty levels enhance metabolic modulation as compared with those with lower difficulty levels, (3) metabolic modulation during motor learning is age dependent, and (4) training-induced metabolic modulation may have a differential effect on motor learning and retention. Young ( n  = 25, 12 females) and older ( n  = 21, 10 females) human adults completed a 6 d motor learning protocol with magnetic resonance spectroscopy scans being administered before, during, and after a low and high task complexity training condition. We observed a training-induced reduction of SM1 GABA+, regardless of age and task difficulty level, but no significant changes in DLPFC. Neither region showed a significant Glx (combined glutamate and glutamine) modulation. In addition, baseline GABA+ levels predicted learning, but this effect was region and task difficulty dependent. Age-related differences emerged in the prediction of retention, with older adults showing a beneficiary role of task-induced increase in the SM1 inhibitory tone. These results highlight the complexity of metabolic dynamics in learning and retention, showing their dependency on age, brain region, and task difficulty.

A Spinal Origin for the Obligate Flexor Synergy in the Nonhuman Primate: Implications for Control of Reaching

Stroke survivors frequently develop the flexor synergy, an obligate cocontraction of shoulder abductors and elbow flexors. The neural substrate has to date proven elusive. Here we trained two healthy female monkeys to generate isometric elbow and shoulder torques to move an on-screen cursor and recorded neuron firing from motor cortical areas and the reticular formation. All regions contained some cells coding for independent contractions about elbow or shoulder. For neurons coding cocontractions, there was a surprising bias: More cells were related to combinations orthogonal to the flexor synergy, e.g., shoulder abduction with elbow extension. We then used threshold microstimulation to examine patterns of muscle activation elicited from the primary motor cortex, reticular formation, and spinal cord in five female monkeys. Only in the spinal cord did microstimulation generate coactivation aligned to the flexor synergy. Our results suggest that primitive spinal circuits are limited to synergistic coactivation, a pattern which perhaps evolved for locomotion. Prehensile reaching movements aligned to these synergies require only limited descending control from the cortex and brainstem. In contrast, reaching orthogonal to the flexor synergy relies heavily on descending drive both to suppress spinal circuits and to sculpt motoneuron activity. The findings suggest that apparently similar reaches in different directions have different neural substrates. After a stroke, loss of descending drive leaves movements limited by spinal motor primitives.

Anesthetic State-Dependent Bidirectional Control of States of Consciousness via Heterogeneous Medial Septum to Ventral Tegmental Area Circuits under Sevoflurane in Mice

General anesthesia (GA) induces reversible unconsciousness for surgery, yet mechanisms underlying bidirectional transitions of states of consciousness during GA remain largely unknown. Here, we focused on states of consciousness rather than contents of consciousness, which reflects the capacity for responsiveness to stimuli. Electroencephalography/electromyography was applied in both male and female mice to investigate states of consciousness during sevoflurane GA. We identified the population activity of glutamatergic neurons in the medial septum (MS) to change synchronously with altered states of consciousness during sevoflurane GA. Activation of glutamatergic MS neurons (MS Vglut2 ) or their projections in the ventral tegmental area (VTA) facilitated behavioral emergence and cortical activation during sevoflurane GA, while their inhibition deepened cortical inhibition. Nevertheless, we further identified anesthetic state-dependent dual control of states of consciousness by monosynaptic innervations from MS Vglut2 neurons to heterogeneous downstream VTA neurons. Specifically, optogenetic activation of MS-innervated glutamatergic VTA neurons promoted cortical activation during both continuous steady-state GA (CSSGA) and burst suppression (BS). With current stimulation protocol, optogenetic activation of MS-innervated dopaminergic VTA neurons promoted cortical activation mainly under CSSGA. Optogenetic activation of MS-innervated GABAergic VTA neurons enhanced cortical inhibition mainly under BS. Our findings reveal an anesthetic state-dependent mechanism where MS Vglut2 neurons bidirectionally regulate states of consciousness through heterogeneous VTA neurons, providing insights to the complexity in the regulation of states of consciousness under GA.