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Children often deny the possibility of unusual and improbable events and immoral actions. Three preregistered experiments on 5- and 6-year-old children (N = 154, 47% female, 53% male, tested across three sites in Canada with varied ethnic compositions between March and September 2025) find that children better recognize that improbable events are possible when the events include agents who could plausibly be involved in them and who might want to produce them. In Experiments 1 and 2, children affirmed possibility more when unusual events were described as involving thematically related agents rather than unrelated or indefinite ones. Children also affirmed possibility more for actions that could be voluntarily chosen than for incidents that might happen involuntarily. In Experiment 3, children affirmed possibility more when improbable events involved agents with relevant motives and locations, but this did not affect children's judgments about the possibility of acting immorally. These findings suggest that children often deny the possibility of improbable events because they fail to recall relevant knowledge useful for envisaging the circumstances behind the events. Young children often say it is impossible for people to do unusual things. For instance, they deny that a person in real life could have a pet zebra. The research reported here shows, though, that children are more likely to say unusual events can happen if they are asked about events that involve people who could plausibly be involved in the events, and who might even want the events to happen. For example, they often say a pet zebra is possible if asked about a zookeeper having one. Specifying a related person may help children imagine how unusual events could occur. Reminding children about zookeepers may help them think about where and how a person could get a pet zebra.

Background. The diagnosis of immediate drug allergy (DA) relies on a combination of skin tests (ST), drug provocation tests (DPT), specific IgE levels (sIgE) and/or basophil activation tests (BAT). We aimed to compare BAT results with those of other allergy tests in patients with suspected immediate DA to a heterogeneous group of drugs, aiming to assess its diagnostic value. Methods. Patients who underwent BAT for suspected immediate DA at our hospital from January 2018 to December 2023 were included. Each case (suspected drug) was classified based on diagnostic tests performed - probable vs. improbable allergy (assessed by ST and/or sIgE only) or confirmed vs. excluded allergy (assessed by DPT). Inter-method agreement was assessed with Cohen's kappa index (κ). Results. Eighty-five patients were included: 51 female (60.0%), median age 53.0 years [interquartile range (IQR) = 33.0, Q1-Q3=31.0-64.0]. Median time elapsed since index reaction was 1.0 year [IQR=3.0, Q1-Q3 = 1.0-3.0]. We identified 112 suspected drugs: out of 16 cases with positive BAT (14.3%), 6 were probable (37.5%) and 1 confirmed allergy (6.3%). From 89 drugs with negative BAT (79.5%), 41 were improbable (46.1%) and 5 excluded allergy (5.6%). Seven agents had an inconclusive BAT (6.3%). A slight agreement (κ = 0.201) between BAT and other studies was observed when combining probable/improbable and confirmed/excluded results (n = 76). When limiting these findings to confirmed/excluded results (n=6), we found a perfect agreement (κ = 1).  Conclusions. We assessed BAT performance in a larger sample than those from previous studies. Slight agreement between methods increased to a perfect agreement when limiting to confirmed cases. Larger studies are needed to establish BAT's diagnostic value.

Understanding broadly neutralizing antibody (bnAb) lineage development in rhesus macaques (RMs) infected with simian-human immunodeficiency virus (SHIV) may inform HIV-1 vaccine designs. We analyzed HIV-1 envelope (Env)-antibody coevolution in 18 RMs infected with SHIV.BG505 (subtype A) and found conserved patterns of antibody recognition and Env escape, including in three animals that developed V3-glycan-reactive bnAbs. From one RM with V3-glycan-targeted plasma Abs that neutralized heterologous HIV-1 strains, we isolated 203 members of a single clonal antibody lineage designated DH1030. DH1030 antibodies demonstrated genetic, functional, and structural similarities with the human V3-glycan bnAb lineage DH270, which was isolated from an individual with subtype C HIV-1 CH848 infection. Human-DH270 and macaque-DH1030 bnAbs shared early improbable mutations in the heavy chain complementarity determining region 2 that were critical for bnAb development. These convergent patterns of antibody evolution, accumulation of key improbable mutations, and mode of epitope recognition were shared across primate species and distinct HIV-1 subtypes, findings that may be leveraged in HIV-1 vaccine designs. Furthermore, our data highlight the value of SHIV-infected macaques as an outbred model system to explore conserved molecular pathways of bnAb development after infection and vaccination.

Humans comprehend language rapidly, with active prediction of upcoming words as a key mechanism. Studies using sentences have documented facilitations in behavior and brain activity (N400) when people encounter predictable words, and brain responses (anterior positivity) specific to prediction violations. However, it has been challenging to investigate prediction formation mechanisms, given the complex, incremental context provided by sentences. Here, we examined prediction by measuring EEG in a simple word stem completion task. Participants saw three initial letters (e.g., bro___) varying in constraint/entropy of possible completions and were asked to generate a word completion. They then saw a target that was either a probable completion (brother), an improbable completion (bronze), or a pseudoword (*brom). In Experiment 1, participants self-reported whether the target matched their prediction; in Experiment 2 they made a lexical decision to the target and then typed in their prediction. Consistent with findings from sentences, N400s were reduced for probable completions, primarily driven by a greater proportion of match responses with highly facilitated N400 amplitudes. No anterior positivity was found to improbable words in Experiment 1, but it was present in Experiment 2. Given these task differences, the anterior positivity may therefore reflect engagement of processes to manage activation of lexico-semantic information when there is competition, as from a strong prediction. Crucially, neural responses following the word stem (i.e., during prediction formation) showed a sustained centro-posterior positivity that was graded with entropy (more negative for high-entropy stems). This effect reveals that prediction-formation processes are sensitive to the distribution of possible completions based on the context.

Harmonic expectation is an important mediator of musical experience. EEG research has identified event-related potential (ERP) components associated with expectation, including the early (right) anterior negativity (E(R)AN), which is theorized to index harmonic surprisal with reference to long-term memory of the statistical structure of music. However, the role of top-down influences on harmonic predictions remains underexplored. One specific influence concerns how a given harmony can be interpreted in different ways, depending on its syntactic role in a musical context. We present data from a novel paradigm that cues listeners to the syntactic structure of the stimuli (but not whether they contain improbable events). Our main result revealed larger E(R)AN amplitudes for improbable chords when listeners knew that additional context would follow a surprising harmony; P3a and P600 amplitudes were also larger in such cases. Using the theoretical framework of predictive coding, we propose that, in such cases, listeners assign higher precision to their predictions, leading to larger prediction errors as indexed by the E(R)AN, P3a, and P600 ERP components, and that prior context alone does not fully explain how unpredictable events are processed. Musical surprisal arises from a dynamic interplay between bottom-up cues and a listener's top-down anticipation within specific syntactic contexts.

Understanding broadly neutralizing antibody (bnAb) lineage development in rhesus macaques (RMs) infected with Simian-HIV (SHIV) may inform HIV-1 vaccine designs. We analyzed HIV-1 envelope-antibody coevolution in 18 RMs infected by SHIV.BG505 (subtype A) and found highly conserved patterns of antibody recognition and Env escape, including in three animals that developed V3-glycan bnAbs. From one RM with V3-glycan targeted plasma breadth, we isolated 203 members of a single clonal Ab lineage designated DH1030. DH1030 Abs demonstrated striking genetic, functional and structural similarities with the human V3-glycan bnAb lineage DH270, which was isolated from an individual with subtype C HIV-1 CH848 infection. Notably, human-DH270 and macaque-DH1030 bnAbs shared early improbable mutations in HCDR2 that were critical for bnAb development. Thus, key improbable mutations and convergent patterns of antibody evolution and epitope recognition were shared across primate species and distinct HIV-1 subtypes, findings that may be leveraged in new HIV-1 vaccine designs. Broadly neutralizing antibodies targeting HIV-1 envelope surface protein develop via a common maturation pathway across primate phylogeny.

In-depth qualitative studies concerning exceptionally gifted mediums are very useful for investigating the occurrence of anomalous information reception, however, there is a dearth of studies with recorded evidence. To investigate the occurrence of anomalous information reception in a recorded session with Chico Xavier, one of the 20th century's leading mediums. Analysis of a 54-minute recording containing the reading of a mediumistic letter, two poems attributed to deceased Portuguese poets, and a dialogue in which Chico Xavier describes 18 deceased personalities. Following the identification of the verifiable information, an exhaustive investigation was carried out to assess the accuracy of the items of information and the likelihood of the medium having had prior access thereto. For the poems, a linguistic-literary, comparative analysis examined convergences and divergences of metre, style and themes between the alleged mediumistic texts and the original works of the authors. The poems analysed show features consistent with the claimed authorship, substantiating this attribution based on textual and comparative criteria. A total of 30 people were identified, with 65 verifiable items of information produced, of which 87.7% were classified as "Correct" and 30.8% as "Highly Improbable" or "Improbable" to have been accessed through conventional means. Conventional explanations are unlikely or highly unlikely for a considerable proportion of the items, particularly those related to Isabel Ramos. Her case is conspicuous, not only for its high degree of accuracy but also for having arisen spontaneously and for being someone who was unknown to the participants, characterising a drop-in case. Considering the complementary, diverse and highly assertive nature of the communications, the survival hypothesis offers the simplest and most parsimonious explanation for what occurred in this meeting.

Children often say that possible events are impossible, and only gradually come to see these events as possible. For instance, they often deny that people could do unusual things, like own a pet peacock, or immoral things, like stealing or lying. These possibility denials are surprising. For instance, children have first-hand experience with the very moral violations they say are impossible. In two experiments (total N = 220), we provide evidence that children's possibility denials can nonetheless be taken at face value and do not merely arise from quirks in how children understand questions about possibility. We do this by showing that these denials also arise in children's judgments of actuality-their judgments about what has actually happened and about which assertions of actual events could be true. In Experiment 1, children aged 4-7 judged whether ordinary, immoral, and improbable events could happen or had ever happened. With both judgments, children mostly responded affirmatively to ordinary events, often responded negatively for immoral events, and mostly responded negatively to improbable ones. In Experiment 2, children aged 5-7 judged if assertions of the three kinds of events could be true, and the same pattern emerged again. Together, these findings show that children's denials of immoral and conceptually improbable events extend beyond their judgments about what is possible and match their inferences about what is actual. These correspondences across judgments suggest that children drew on a single procedure, or set of procedures, for assessing possibility. SUMMARY: We show that children judge unexpected events as both impossible and nonactual. Four- to seven-year-olds judged if events could happen, if events had ever happened, and if assertions about events could be true. For all judgments, children often responded negatively to immoral events, and mostly responded negatively to conceptually improbable ones. Children's possibility denials can be taken at face value, and do not reflect quirks in how they respond to questions about possibility.

Numerous unidentified white blobs were discovered along Ship Cove Beach, Newfoundland, Canada, in September 2024. Fueled by national and international media coverage and public speculation, this incident raised concerns about potential health, safety, and environmental impacts. A comprehensive forensic analysis was conducted using physicochemical characterization, spectroscopy, mass spectrometry, and elemental analysis to determine the composition, nature, and possible origin of the material. The chemical fingerprinting results indicate the following: (1) the sample is unlikely to be petroleum-derived or contaminated by petroleum products; (2) biodiesel is improbable due to the absence of significant fatty acid methyl esters; (3) the material does not appear to be silicone-based or chlorinated (e.g., silicone sealants or chlorinated vinyl compounds); (4) the presence of aldehydes, fatty acids, and plant-derived sterols-coupled with the absence of cholesterol-suggests a plant oil-based origin; (5) high molecular weight compounds and thermal transformation behavior point to the presence of polymeric materials; and (6) the substance is neither flammable, combustible, corrosive, oxidizing, nor radioactive. These findings contribute to understanding the nature of the spill and highlight the utility of multidisciplinary forensic approaches in environmental incident response.

Life requires genetic information to maintain a stable, highly ordered state far from thermodynamic equilibrium, but the general principles and specific mechanisms governing these dynamics are not well established. Here, the role of information in maintaining the unique thermodynamic state of living systems is examined in enzyme-accelerated reactions. Thermodynamically, reaction rates are governed by temperature and activation energy in the empirically derived Arrhenius equation. Living systems use genetically encoded enzymes to accelerate reactions up to 15 orders of magnitude without increased temperature. This is quantified in the Arrhenius equation as decreased activation energy but achieved physically by optimizing quantum interactions of substrate molecules to increase the probability of reaction. This scale transition from molecular mechanics in the information encoded amino acid sequence to quantum mechanics in substrate interactions represents "fine graining" which, as the opposite of coarse graining, requires added information. This is hypothesized to emerge from the cell's molecular machinery that controls folding kinetics to ensure (with high probability) the genetically encoded string of amino acids folds to a single enzymatically functional 3-dimensional configuration from all other thermodynamically possible states thus increasing Shannon information. Enzyme-accelerated reactions alter concentrations of substrate and products without increased temperature to generate a Boltzmann distribution that is highly improbable for, and therefore, not in equilibrium with the cell's thermodynamic state (temperature). Failure to maintain this non-equilibrium results in death, enabling evolutionary feedback. Furthermore, since protein function governs organism fitness, evolutionary selection is applied to both the gene that encodes the protein and cellular mechanisms that control its folding. By altering probabilistic quantum states during chemical reactions and producing statistical mechanics (Boltzmann distribution) inconsistent with the cellular thermodynamic state, the probability functions of Shannon information in the genome act at microscopic/macroscopic interfaces to enable the ordered, non-equilibrium state necessary for life.

Based on twelve boreholes to groundwater on a meltwater plain in Jutland, Denmark, we document that the 87Sr/86Sr ratio of the groundwater is significantly higher in the pristine areas of heath and forests than in the adjacent farmland areas. The average ratio is 0.70798 in the farmland areas versus 0.71490 in the pristine areas. The sand of the vadose zone exhibits even larger differences with average values of 0.70959 in the farmland and 0.72205 in the pristine land. The strontium concentrations show similar changes, although the highest values here are found in the farmland areas. As the study area consisted entirely of pristine heathland until around 1900, the 87Sr/86Sr values, at that time must have been equally high everywhere. Today, only the pristine areas exhibit high values, whereas the values from the farmland are low. Strontium derived from agricultural lime is the only possible source for these low values. They cannot be caused by strontium from carbonate clasts buried deeper in the meltwater deposits, as it has previously been suggested. Such a hypothesis would require that the clasts were concentrated in the central farmland area and absent in the pristine areas, a highly improbable explanation considering the homogeneous geology of the plain. The new results confirm that strontium released from agricultural lime is highly mobile and not retained in the topsoil of the farm fields as earlier suggested. Ground- and surface waters in contact with farmland should consequently be avoided in the creation of strontium baselines.

Mito Thermo Yellow (MTY) is a mitochondrially targeted fluorophore that shows marked fluorescence quenching with increasing temperature, allowing for interrogating temperature dynamics in the mitochondria of live cells. Here we re-evaluate published MTY fluorescence responses used to argue in favor of the 'hot mitochondria' concept; the assertion that mitochondria operate while maintaining substantial (> 10°C) apparent temperature gradients (ΔTapp) between themselves and their cellular environment. We find that MTY fluorescence kinetics are incompatible with the expected dynamics of mitochondrial heat production and diffusion. We further explore the published effects of mitochondrial inhibitors on MTY, and related evidence for ΔTapp of > 10°C, again concluding results are inconsistent with the expected heat production dynamics. Thus, assertions of ΔTapp > 10°C between mitochondria and their cellular environment based on MTY fluorescence intensity changes are unlikely to be reporting a signal that is uniquely intramitochondrial temperature. In addition to these analyses, we further argue that the inference mitochondria can operate at an internal temperature of > 48°C, as reported using MTY, is improbable as these internal temperatures would cause protein denaturation and aggregation and induction of the heat shock (HSR), unfolded protein (UPR), and integrated (ISR) stress responses. Taken as a whole, we conclude MTY and similar tools must be re-evaluated in regard to if they are providing solely information on local temperature and thus are so far inadequate, unto themselves, to demonstrate the existence of hot mitochondria.

Following initially successful resuscitation and the achievement of a spontaneous rhythm, patients are mostly comatose and are transferred to the intensive care unit. The brain is particularly vulnerable for injuries under global ischemia or hypoxia and therefore severe brain damage without damage to other organs is a frequent occurrence. This is referred to as hypoxic-ischemic encephalopathy (HIE) and preferentially affects neurons in the cerebral cortex, the basal ganglia and the cerebellum. The brain stem is less vulnerable. The unresponsive wakefulness syndrome (UWS), previously known as apallic syndrome or vegetative state, is a frequent form of HIE and can persist for years in a ventilation nursing home. In many patients multimodal neurological prognostication enables a reliable prediction on whether a relevant recovery of cerebral function is likely or impossible, even during the stay in the intensive care unit. These include the clinical neurological examination after a sufficiently long observational time of mostly at least 72h, cerebral imaging, i.e., cranial computed tomography (cCT), if necessary cranial magnetic resonance imaging (cMRI), electrophysiological examinations (electroencephalography, EEG), median nerve somatosensory evoked potentials (SSEP) and determination of blood biomarkers (neuron-specific enolase, NSE, neurofilament light chains, NFL). Findings that make a severe HIE very likely are a bilateral lack of pupillary light reflex 72h after resuscitation, bilateral absence of cortical median nerve SSEP, highly malignant EEG pattern, NSE levels > 90 ng/ml and a lack of gray-white differentiation of the cerebrum in cCT. A normal NSE or NFL level 48-96h after resuscitation, an early continuous EEG with responses to external stimuli, high amplitudes of the median nerve SSEP and a normal cMRI make a severe HIE improbable. If the short-term clinical course and the prognostic investigations do not provide a clear determination of the extent of the HIE, a time-limited trial of a neurological early rehabilitation can clarify the question whether regaining consciousness with relevant cognitive functions occurs or not. Nach zunächst erfolgreicher Reanimation mit Erreichen eines spontanen Rhythmus sind Patient:innen zumeist komatös und werden auf eine Intensivstation aufgenommen. Das Gehirn ist besonders vulnerabel für Schädigungen unter globaler Ischämie bzw. Hypoxie und eine schwere Hirnschädigung ohne schwere Schädigung anderer Organe daher häufig. Diese wird als hypoxisch-ischämische Enzephalopathie (HIE) bezeichnet und betrifft präferenziell Neurone im Großhirnkortex, den Basalganglien und im Kleinhirn. Der Hirnstamm ist weniger vulnerabel. Das Syndrom der reaktionslosen Wachheit (SRW), früher als apallisches Syndrom oder „vegetative state“ bezeichnet, ist eine häufige Ausprägungsform der HIE und kann bei Pflege in einem Beatmungsheim über Jahre persistieren. Eine multimodale neurologische Prognosediagnostik ermöglicht bei vielen Patient:innen noch während des Aufenthalts auf der Intensivstation eine sichere Vorhersage darüber, ob eine relevante Erholung der Großhirnfunktion sehr wahrscheinlich oder ausgeschlossen ist. Die Diagnostik umfasst die klinisch-neurologische Untersuchung nach einer ausreichend langen Beobachtungszeit von meist mindestens 72 h, die zerebrale Bildgebung (kranielle Computertomographie [cCT], gegebenenfalls kranielle Magnetresonanztomographie [cMRT]), elektrophysiologische Untersuchungen (Elektroenzephalographie [EEG], somatosensorisch evozierte Potenziale [SSEP] des N. medianus) sowie die Bestimmung von Blutbiomarkern (neuronenspezifische Enolase [NSE], Neurofilamentleichtketten [NFL]). Befunde, die eine schwere HIE sehr wahrscheinlich machen, sind eine bilateral fehlende Pupillenlichtreaktion 72 h nach Reanimation, bilateral fehlende kortikale Medianus-SSEP, Highly-malignant-EEG-Muster, NSE-Werte > 90 ng/ml sowie eine aufgehobene Grau-Weiß-Differenzierung des Großhirns in der cCT. Eine normwertige NSE oder NFL 48–96 h nach Reanimation, ein frühzeitig kontinuierliches Elektroenzephalogramm mit Reaktivität auf Außenreize, hohe Amplituden der Medianus-SSEP und eine unauffällige cMRT machen eine schwere HIE unwahrscheinlich. Lassen der kurzfristige klinische Verlauf und die prognostischen Untersuchungen keine sichere Bestimmung des Ausmaßes der HIE zu, kann ein „time-limited trial“ einer neurologischen Frührehabilitation die Frage klären, ob ein Wiedererwachen mit relevanten kognitiven Funktionen eintritt oder nicht.

This study employed the magnetic field-mediated/gum arabic to prepare low-salt myofibrillar protein (MP) gel and simulated the oral processing of interactions between MP and mucin on the perception of saltiness. The results indicated that the amalgamation of magnetic fields and gum arabic effectively promoted the release of sodium ions, enhanced the apparent viscosity of MP, and increased its binding affinity with mucin. Consequently, this resulted in the prolongation in the retention time of MP on the tongue surface and ultimately improved the perception of saltiness. Besides, spontaneous endothermic interactions occurred between MP and mucin, which primarily dominated by hydrophobic interactions that induced changes in the structure of MP, such as the occurrence of disulfide bonds. However, it was improbable that there would be direct bonds between mucin and MP. In summary, magnetic field-mediated/gum arabic promoted sodium ions to interact with taste receptors to generate stronger salty taste signals.

AP-1 transcription factors are a network of cellular regulators that combine in different dimer pairs to control a range of pathways involved in differentiation, growth, and cell death. They dimerize via leucine zipper coiled-coil domains that are preceded by a basic DNA binding domain. Depending on which AP-1 transcription factors dimerize, different DNA sequences will be recognized resulting in differential gene expression. The affinity of AP-1 transcription factors for each other dictates which dimers form. The relative concentration of AP-1 transcription factors varies with tissue type and environment, adding another layer of control to this integral network of cellular regulation. The development of artificial intelligence (AI)-based protein structure prediction methods gives us a new technique to investigate or predict how dimerization affects combinatorial control. All versions of AlphaFold2 and AlphaFold3 are AI/deep learning programs that predict 3D structures of proteins from an amino acid sequence and multiple sequence alignments of homologous proteins. To fully realize the potential of AI for structural biology, it is essential to understand its current capabilities and limitations. In this study, we used the classical example of an AP-1 dimer: Fos and Jun, and an array of over 2000 experimentally tested human leucine zippers to interrogate how AlphaFold models leucine zipper domains and if AlphaFold can be used to differentiate between probable and improbable dimer interfaces. We found that AlphaFold predicts highly confident leucine zipper dimers, even for dimer pairs such as the FosB homodimer, for which electrostatics are known to prevent their formation in vivo. This is an important case study concerning high-confidence but low-accuracy protein structure prediction.