搜索结果：Surprising

While somatic mitochondrial dysfunction occurs in diverse cancers, the association between oncogenesis and germline mitochondrial gene pathogenic variants remains unclear. Further, few clinical observations have been reported of cancer occurring in primary mitochondrial disease (PMD) patients. To improve understanding of the potential modulating role for PMD gene disorders in cancer prevalence. 727 individuals, including 100 with PMD, from 97 unrelated families were retrospectively surveyed to assess their history of individual cancer occurrence. We evaluated survey responses by characterizing the cancer prevalence among the study cohort and comparing to the general U.S. population via the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database. Odds ratio calculation was performed to determine the association of survey responses and cancer prevalence. Although overall cancer prevalence in PMD probands and their families was elevated compared to the NCI SEER rate (8800 vs 5600 cases per 100,000), odds ratio calculation determined that PMD did not significantly increase the likelihood of developing cancer, with a non-significant trend observed toward less cancer occuring in PMD that needs to be explored in further studies. Cancer prevalence was significantly correlated with advanced age. Significantly reduced prevalence of prostate cancer was seen across the entire cohort. Surprisingly, while low absolute prevalence (n = 3), a 9-fold increased odds ratio of cancer was seen in POLG patients relative to those with other causes of PMD. No evidence of increased cancer odds was identified in a cohort of PMD patients and their close relatives. Interestingly, a possible inverse association, which did not reach statistical significance, was suggested between mitochondrial disease status and cancer odds. Future prospective investigations in larger PMD kindreds are warranted to validate and evaluate potential mechanistic relations between cancer prevalence and PMD. No increased odds ratio but rather a non-significant trend toward inverse relationship between cancer and primary mitochondrial disease was observed in a retrospective cohort survey study, based on which future studies are warranted. Mitochondria are key organelles in our cells that make energy, help control cell death, and regulate the production of reactive oxygen species. Because of these roles, scientists have long suspected that mitochondrial dysfunction might influence cancer development. Tumors often show abnormal mitochondrial activity, but it is unknown whether people who are born with inherited mitochondrial disorders—called primary mitochondrial diseases (PMD)—are more or less likely to develop cancer. PMD includes many different inherited conditions caused by gene changes in either mitochondrial or nuclear DNA. Although cancer cells often acquire mitochondrial mutations, inherited mitochondrial gene changes that impair mitochondrial energy production in the respiratory chain have not been shown to strongly increase cancer odds. To explore this question, we collected health information from 727 individuals across 97 families, including 100 people with PMD. We compared how often cancer occurred in these families to cancer rates from the National Cancer Institute. We also observed whether having PMD, carrying a PMD disease gene variant, or relation to someone with PMD affected a person’s likelihood of developing cancer. A higher overall cancer prevalence was seen in PMD families compared to the general population that appeared attributable to advanced age, as older adults had higher cancer rates regardless of PMD status. Importantly, PMD status did not increase the likelihood of developing cancer. Rather a non-significant trend was observed toward a negative association. One surprising exception was that individuals with POLG-related PMD showed a higher odds ratio of cancer compared to those with other PMD types, although the affected patient number was small and absolute prevalence remained low. Collectively, these results did not reveal a statistically significant association between primary mitochondrial disease and cancer prevalence. Larger studies are needed to confirm these findings and understand whether and how inherited mitochondrial dysfunction might influence cancer development.

Understanding human-driven environmental impacts on microbial community distribution, abundance, and function remains a central challenge in microbial ecology. In particular, the drivers of temporal succession in community membership following perturbation remain unclear. Great Salt Lake, Utah, bears clear hallmarks of human disturbance, including a rock-filled railroad causeway that sequestered its northern arm from freshwater river influx, leading to localized hypersalination and food web collapse. Following decades of riverine water diversion, the southern arm of this terminal lake reached a historic low elevation during a time of increased climatic change, placing strong environmental pressure on the robust saline ecosystem. Here, we use molecular methods to report microbial community composition during this severe drought year at sites across the lake, including where the north and south arm waters contact. At sites of hypersaline water intrusion, we observe surprising stability in the north arm community composition, in contrast with strong perturbation in the south arm community structure. We use hydrodynamic modeling to pinpoint physical water flow dynamics as a key driver of these community shifts. At hypersaline north arm sites far from hyposaline water intrusion, abundance shifts were detected in predatory and parasitic taxa, a discovery that reveals surprising ecological dynamics in saturated hypersaline systems. In sum, this study demonstrates drastic hypersaline microbial community shifts during salinity and extreme weather perturbations. The Great Salt Lake ecosystem is rapidly drying due to climate warming and human consumptive water use that diverts riverine input to the lake's south arm. In 2022, the lake dried to reach its lowest elevation in recorded history, dehydrating microbial mats and exposing the toxic dust of the lakebed. This endangers food webs, industry, and human health. In response, Utah agencies are regulating Great Salt Lake salinity with ongoing adaptive structural engineering interventions. We hypothesized that these interferences would lead to dynamic mixing of microbial communities across a salinity gradient. We find that physical mixing drives dynamic, ongoing diversity loss and food web disruption at these sites of intervention, providing insights into how salinity regulation could be improved.

Introduction Severe aplastic anemia (SAA) is a bone marrow failure disorder characterized by profound pancytopenia associated with a high risk of infection and bleeding. Case Presentation We report a case of a 19-year-old patient with a history of acute hepatitis who was admitted to the hospital with acquired SAA attested by 2% cellularity at bone marrow trephine biopsy. In the absence of matched sibling donor, immunosuppressive therapy with horse anti-thymocyte globulin, cyclosporin and eltrombopag was initiated. Following centrifugation, serum obtained from blood samples addressed to the laboratory displayed a rare manifestation of brown color. Intravascular hemolysis was excluded based on normal haptoglobin and lactate dehydrogenase ranges, although bilirubin was mildly elevated. The brown staining disappeared after therapy discontinuation. Eltrombopag is a chromogenic molecule which absorbs visible light associated with serum coloration. Conclusion This rare case highlights drug-induced serum pigmentation as a surprising manifestation in patients receiving eltrombopag and its normalization following drug withdrawal.

People are often faced with surprising events that defy expectations. Such events elicit transient activity in the locus coeruleus/norepinephrine system and elevation of peripheral arousal markers including pupil dilation and a late positive peak in stimulus evoked EEG response, the P300, but the function of these signals remains unclear. We propose that they reflect latent state transitions that dynamically control the mental context governing learning and perception. We tested and confirmed five preregistered predictions of this theory using EEG and pupil measurements collected from people performing a colour prediction and reproduction task. Task-induced latent state transitions elicited pupil dilation and amplified event-related potentials including the P3a component of the P300. These EEG and pupil measures related to behavioural signatures of latent state updating, including reduced bias and bidirectional adjustment of learning, both across trials and across individuals. Our findings support the theory that locus coeruleus/norepinephrine-linked arousal systems optimize behaviour by signalling environmental transitions to facilitate rapid adjustments of mental context.

Mitigation measures are essential for controlling the spread of infectious diseases during pandemics and epidemics, but they impose considerable societal, individual, and economic costs. We developed a general framework that combines simulation of disease dynamics with optimal control to determine mitigation strategies that balance infection and mitigation costs. Optimizing this trade-off, we identified three surprising effects: first, assuming a constant reproduction number [Formula: see text], the optimal response is typically "all-or-nothing": depending on disease severity, either strict mitigation or none at all is optimal, with intermediate levels emerging only in restricted regimes that we characterize analytically. Second, under seasonal variations, optimal mitigation is stricter during winter. Interestingly, a single wave of infections still arises in spring, replacing the autumn/winter waves known for classical influenza. Third, during steady vaccination campaigns, even optimal mitigation can result in transient infection waves. Finally, we quantify the cost of delayed mitigation onset and show that even short delays can substantially increase total costs-if the disease is severe. Overall, our framework is easily applicable to general and complex settings and thereby presents a versatile tool to explore optimal mitigation strategies for endemic and pandemic infectious disease.

Overly long or effortful utterances are interpreted as carrying more information than short or easy ones-a phenomenon known as manner implicatures in pragmatics. Can this mechanism guide the interpretation of unfamiliar words? In seven studies testing adults (N = 1,762) and children (N = 282), participants had to pair two words in an unknown language (e.g., "elco" and "ajajata") with two referents, one more prototypical than the other (e.g., a green crocodile and a yellow crocodile). The less prototypical referent is less expected and more surprising; thus, the action of referring to it carries more information than the action of referring to the more prototypical referent. We predicted that shorter words would be preferentially paired with prototypical referents. This effect was verified on adult participants inside and across 18 languages and held even when participants explicitly claimed to have used no strategy at all. Varying the respective prototypicality of the stimuli did not measurably change this effect: Adult participants responded similarly to a large differential in prototypicality as to a more moderate one. French children aged 3 to 11 also showed the predicted effect, with little discernible effect of age. Consistent with manner implicatures, adult participants (across four languages) and French children also show the predicted effect when the phonotactic complexity of words is manipulated instead of their length. Thus, manner implicatures guide the interpretation of unfamiliar words by children and adults. These results are consistent with the view that costlier messages are generally interpreted as carrying more information. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Depression has been linked to reduced size of subcortical regions and abnormal functional connectivity in frontal and default mode networks. However, recent meta-analyses have failed to identify significant converging correlates of depression across the literature such that a conclusive mapping of the neuroimaging correlates of depression remains elusive. We leveraged 23,417 participants across 6 population datasets to comprehensively establish the neuroimaging correlates of depression. We found reductions in gray matter volume/cortical surface area associated with depression in the frontal cortex, anterior cingulate and insula, confirming previous studies showing the importance of prefrontal and default mode regions in depression. Our findings demonstrate multiple surprising results, including a lack of depression correlates in subcortical brain regions and significant depression correlates in somatomotor and visual regions. Overall, these results shed new light on key brain regions involved in the pathophysiology of depression, updating our understanding of the neuroimaging correlates of depression symptoms.

Hexagonal perovskite oxides with 12R stacking host well-separated face-sharing octahedral metal trimers with short metal-metal distances, leading in some cases to large degrees of magnetic frustration and cluster magnetism. Introducing magnetic ions in proximity to these trimers can influence the degree of frustration and cluster magnetism, but the extent to which the magnetism can be tuned by varying neighboring metal cations remains an open question. In this work, we test the impacts of using Nd in proximity to Mn trimers in the hexagonal perovskite 12R-Ba4NdMn3O12-γ. Given this stoichiometry, Nd should assume the 4+ oxidation state with a spin state of S = 1, which would be the first realization of Nd4+ in an oxide environment. Through detailed bulk magnetic, X-ray absorption spectroscopic, and powder neutron diffraction (PND) measurements, we find that Nd4+ is realized in this material, but there is also partial reduction to Nd3+, which is charge-balanced by O vacancies. Magnetometry measurements indicate an antiferromagnetic ordering temperature TN ≈ 16 K, and PND measurements reveal a surprising collinear antiferromagnetic structure with magnetic space group Pc2/m (no. 10.49 in BNS notation), which has not previously been seen in this class of materials. Our results represent a comprehensive analysis of the structural, electronic, and magnetic properties of 12R-Ba4NdMn3O12-γ, showing the first observation of partial Nd4+ in an oxide, and demonstrating that this structural class can host a broad range of magnetic structures which are not easily predicted based on compositional trends.

Congenital heart defects (CHDs) comprise the most common congenital malformation affecting nearly 1% of all newborns. In individuals with sex chromosome aneuploidy syndromes, however, the prevalence reaches up to 50% of all livebirths. One commonality to these syndromes is a marked reduction in sex hormones, particularly androgens. Androgen receptor (Ar) insufficiency represents a culprit in the pathophysiology of adult onset cardiovascular disease and arrhythmia, but there are no reports regarding Ar function during heart development. This is surprising as androgens along with its nuclear receptor exist already during early development, even before gonads develop and become functional. We evaluated the role of the Ar during vertebrate heart development by generating loss-of function in zebrafish embryos via pharmacological inhibition, transient CRISPR/Cas9 treatment, or interference of splicing as well as murine cell culture. Attenuation of Ar function in zebrafish embryos prevents normal cardiac morphology and physiology as apparent by edema, bradycardia and arrhythmia. Molecularly, we identified increased abundance of adrenomedullin (Adm) 2a as a likely cause for the observed defects. Cellularly, these phenomena may be linked to impaired formation of proepicardial cells, which are reported to intermingle with cells of the conduction system and influence cardiac pacing. A disrupted Ar - Adm2 axis possibly contributes to the increased frequency of CHD in individuals suffering from sex chromosome aneuploidy syndrome. Testosterone function is generally mediated by androgen receptors in the nucleus of the cell. Interestingly, the androgen receptor exists already in early embryos, long before sexual maturation will be initiated. This study aimed to investigate the function of the androgen receptor during heart development using zebrafish embryos. Embryos lacking functional androgen receptors display severely impaired heart development resulting in a slower and irregularly beating heart. Consistently, several important structures of the heart including the conduction system necessary for cardiac rhythmicity fail to form and function properly in the absence of androgen receptor function. Loss of androgen receptor function leads to elevated expression of adrenomedullin 2a, which has previously been implicated in heart development and function. Consistent with a study reporting adrenomedullin 2a originating from the proepicardium loss of proepicardial genes could be observed in the absence of the androgen receptor. Taken together, this study identifies a novel role of the androgen receptor during early heart development, most likely independent of the later biological sex.

While the influence of the exterior hydrophobicity of ligands conjugated to nanomaterial surfaces on biological applications has been extensively studied, little attention has been given to the impact of the interior hydrophobicity of these conjugated ligands. In this study, we systematically functionalized the surfaces of molybdenum disulfide quantum dots (MoS2 QDs) with different ligands having oligo(ethylene glycol) (EG) tethers of varying length. This will expose the interior hydrophobicity, maximum in the case of No-EG and minimum for Tetra-EG. Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (E. faecalis), and Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (PA), were employed as model organisms to investigate the impact of exposure of interior ligand hydrophobicity on bacterial membrane interactions. Successful surface modification of MoS2 QDs with the ligands was confirmed via zeta potential measurements and Fourier-transform infrared spectroscopy (FT-IR). Antibacterial assays demonstrated that MoS2 QDs functionalized with ligands possessing higher exposure of interior hydrophobicity (No-EG-MQD) exhibited the most potent antibacterial activity, with an exceptionally low minimum inhibitory concentration (MIC) of 15 ng mL-1. In contrast, MoS2 QDs functionalized with ligands exhibiting the least exposure of interior hydrophobicity (Tetra-MQD) displayed the lowest antibacterial activity, with an MIC exceeding 12 000 ng mL-1. The antibacterial efficacy ranked as follows: No-EG-MQD > Mono-MQD > Di-MQD > Tri-MQD > Tetra-MQD. Mechanistic studies revealed that antibacterial activity was governed by a balance of membrane depolarization, membrane rupture, and cellular internalization. In another surprising observation, the toxicity of No-EG-MQD is much lower than that of EG-functionalized MQDs. These exceptional observations can be implemented in many other systems for related biological applications. After observing successful antibacterial activity and lower toxicity in vitro, we have tested their efficacy in vivo by treating a bacterially infected wound in a mouse to investigate additional biological impacts related to ligand hydrophobicity.

Importance: Most couples who turn to assisted reproductive technology (ART) treatment do so, usually, after giving up emotionally on the chances of conceiving naturally. Others undergo ovulation induction with intrauterine insemination (IUI) and turn to ART after the latter has failed. Spontaneous conception after having experienced the exhausting process of ART, whether it was successful or not, could be very surprising and confusing for many couples. Objective: Review all the scenarios within which an unexpected spontaneous conception can occur and the likelihood of its occurrence. These are four such scenarios: (1) after being referred to ART but before the actual initiation of ART; (2) between ART cycles; (3) after a successful ART pregnancy; (4) after giving up on treatment. We have found only a systematic review on #3, but not the other three. Evidence Review: We collected all PubMed citations for the terms "spontaneous conception" and ART or IVF. Thereafter, we realized that no AI tool can filter only the relevant literature. Hence, we exhausted all possible cross-references by manual search to ensure the completeness of the search. Findings: In each of the four scenarios, spontaneous conceptions occur. Before treatment, a critical element is the length of the waiting time, as is the gap between treatments when already treated, with the cost of treatment being a critical determinant. After the conclusion of treatment, whether successful or failed, the main determinants of the chance for spontaneous conception are age, length of infertility, and the leading etiology for infertility. Overall, the chances range from as little as 2% and up to 25%, with severe male factor and a woman's age being the most notable for low rates. Conclusion and Relevance: Each couple entering ART treatment should be informed of the chances for spontaneous conception, whether as an aid to the decision to enter or the decision to leave after a failure, and on the more cheerful side, to be aware of the chances for unplanned pregnancy after a successful treatment.

Reactive oxygen species (ROS) are a pervasive feature of human cancers, yet the protein targets through which ROS-regulated cell states shape tumor biology remains poorly understood. Here, using cysteine chemical proteomics, we define signatures of protein states under distinct cellular ROS environments that capture protein oxidation and conformational changes. Quantifying these signatures in primary lung tumors and brain metastases revealed a surprising enrichment of oxidative states in metastasis. To determine how these states support fitness, we performed genome-wide CRISPR screens and identified the mitochondrial Complex I subunit NDUFA10 as a key oxidation-dependent vulnerability. Oxidation of NDUFA10•Cys253 supports Complex I function through a previously unrecognized nucleotide kinase activity that maintains mitochondrial DNA levels. Enforcing a reduced conformation in NDUFA10 disrupts brain metastatic colonization in vivo . These findings establish ROS regulated protein states as a functional layer of tumor fitness, providing a framework for identifying redox-dependent mechanisms that support cancer progression.

High-throughput microscopy enables large-scale analysis of cancer spheroid interactions. Integrating this technique with point-spread function (PSF) engineering, a customized modification of the optical system, provides 3D imaging capabilities that enable volumetric analysis of the samples from a minimal number of images, thereby reducing phototoxicity and improving temporal resolution. However, existing methods for extracting volumetric information using PSF engineering have been demonstrated primarily on point sources or rely on supervised training data, limiting their general applicability to complex biological samples. Here, we reveal a unique symmetric spheroid-fibroblast interaction pattern using high-throughput imaging. We further characterize these interactions using a PSF-engineered high-throughput microscope, introducing unsupervised methods for 3D localization from single or dual image acquisitions. Our analysis uncovers surprising spatial cellular trajectories of fibroblasts as they approach and interact with spheroids. It further identifies a characteristic 3D distance between adjacent fibroblast clusters and enables live detection of drug-induced perturbations to these interaction patterns.

Turtles are unique among living vertebrates in that their body is protected by a shell, but what the first turtle looked like has remained controversial. A new study reappraises the status of Eunotosaurus - the iconic 'missing link' in turtle evolution - with surprising results.

This study investigated drivers' responses to three types of driving hazards (anticipation, complexity, and surprise) during a simulated drive, considering variations in hazard perception, cognitive load, cue utilisation, and visual attention. Drivers recorded the shortest brake response distances for anticipation (i.e. cued) hazards, intermediate distances for complexity (i.e. multi-cue) hazards, and the longest for surprise (i.e. uncued) hazards. Although cognitive load did not differ across hazard types nor levels of cue utilisation, attention metrics such as fixation duration and time to first fixation varied significantly depending on hazard predictability and complexity. Cue utilisation did not influence cognitive load nor visual attention but was associated with earlier braking responses for complexity hazards, suggesting its relevance in situations requiring the integration of multiple cues. These findings may inform driver training programs and advanced driver assistance systems by supporting interventions that align with drivers' perceptual-cognitive abilities and the demands of different driving environments. Drivers who are better at using visual cues braked earlier for complex, multi-cue hazards, not for predictable or completely surprising ones. Training and driver-assistance systems should prioritise cue use and flexible responding in busy traffic situations where several possible hazards compete for drivers’ attention.

Background/Objectives: Dopamine is well known for its role in reward learning, where phasic activity encodes prediction errors and supports the formation of cue-outcome associations. More recently, dopamine has been implicated in encoding salience, novelty, and aversive events, suggesting a broader function in shaping learning and memory across motivational contexts. However, how accumbal dopamine contributes to the recovery of extinguished fear, a process central to relapse in anxiety and trauma-related disorders, remains unclear. Methods: Here, we examined NAc core dopamine dynamics during shock-induced reinstatement of an extinguished fear memory. Using dLight fiber photometry, we found that a sustained decrease in baseline dopamine marked extinction recall. In contrast, an unexpected reminder footshock prevented this reduction, maintaining dopamine levels near baseline as freezing behavior re-emerged. Results: The reminder shock also evoked a transient dopamine peak, and optogenetic manipulations demonstrated that dopamine signaling during this period bidirectionally modulated reinstatement, with enhancement of dopamine release increasing reinstatement and inhibition of dopamine terminals markedly attenuating it. Together, these results demonstrate that unexpected aversive events reset NAc core dopamine levels and gate the return of extinguished fear. Conclusions: By revealing that accumbal dopamine contributes to fear recovery, this work broadens current models of dopamine function and identifies a neural mechanism through which surprising events may promote relapse of aversive memories in anxiety- and stress-related disorders.

Most publications on the water fleas (Crustacea: Cladocera) have focused, and continue to focus, on the genus Daphnia O.F. Müller, 1785 which represents a model for several branches of recent biological sciences. In contrast, the number of publications on other numerous genera remains minimal. We have revised the Pleuroxus aduncus species group (Anomopoda: Chydoridae), very common in the littoral zone of different continental water bodies of Northern Eurasia. Our study is based on both morphological analysis and molecular phylogenetic data (sequences of the mitochondrial COI and 16S, and nuclear 18S and 28S fragments). P. aduncus (Jurine, 1820) was redescribed based on European material; a new taxon, P. korovchinskyi sp. nov., was described from Eastern Siberia. Our results support the paraphyly of the aduncus group and led to a surprising conclusion: P. truncatus (O.F. Müller, 1785), a very characteristic taxon having a continuous row of denticles along its posterior valve margin, appeared within the morphologically generalized P. aduncus group. This situation has an analog in North America, where the denticulated taxon P. procurvus Birge, 1879 also was differentiated within a group of species lacking such denticles at the posterior valve margin. Our study has demonstrated that we need to continue a program of chydorid revisions, as well as of other "widely distributed" cladocerans.