Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual prediction tendencies do not generalize across modalities

Predictive processing theories, which model the brain as a “prediction machine”, explain a wide range of cognitive functions, including learning, perception and action. Furthermore, it is increasingly accepted that aberrant prediction tendencies play a crucial role in psychiatric disorders. Given this explanatory value for clinical psychiatry, prediction tendencies are often implicitly conceptualised as individual traits or as tendencies that generalise across situations. As this has not yet explicitly been shown, in the current study, we quantify to what extent the individual tendency to anticipate sensory features of high probability generalises across modalities. Using magnetoencephalography (MEG), we recorded brain activity while participants were presented a sequence of four different (either visual or auditory) stimuli, which changed according to predefined transitional probabilities of two entropy levels: ordered vs. random. Our results show that, on a group-level, under conditions of low entropy, stimulus features of high probability are preactivated in the auditory but not in the visual modality. Crucially, the magnitude of the individual tendency to predict sensory events seems not to correlate between the two modalities. Furthermore, reliability statistics indicate poor internal consistency, suggesting that the measures from the different modalities are unlikely to reflect a single, common cognitive process. In sum, our findings suggest that quantification and interpretation of individual prediction tendencies cannot be generalised across modalities.
FHF2 phosphorylation and regulation of native myocardial NaV1.5 channels

Phosphorylation of the cardiac NaV1.5 channel pore-forming subunit is extensive and critical in modulating channel expression and function, yet the regulation of NaV1.5 by phosphorylation of its accessory proteins remains elusive. Using a phosphoproteomic analysis of NaV channel complexes purified from mouse left ventricles, we identified nine phosphorylation sites on Fibroblast growth factor Homologous Factor 2 (FHF2). To determine the roles of phosphosites in regulating NaV1.5, we developed two models from neonatal and adult mouse ventricular cardiomyocytes in which FHF2 expression is knockdown and rescued by WT, phosphosilent or phosphomimetic FHF2-VY. While the increased rates of closed-state and open-state inactivation of NaV channels induced by the FHF2 knockdown are completely restored by the FHF2-VY isoform in adult cardiomyocytes, sole a partial rescue is obtained in neonatal cardiomyocytes. The FHF2 knockdown also shifts the voltage-dependence of activation towards hyperpolarized potentials in neonatal cardiomyocytes, which is not rescued by FHF2-VY. Parallel investigations showed that the FHF2-VY isoform is predominant in adult cardiomyocytes, while expression of FHF2-VY and FHF2-A is comparable in neonatal cardiomyocytes. Similar to WT FHF2-VY, however, each FHF2-VY phosphomutant restores the NaV channel inactivation properties in both models, preventing identification of FHF2 phosphosite roles. FHF2 knockdown also increases the late Na+ current in adult cardiomyocytes, which is restored similarly by WT and phosphosilent FHF2-VY. Together, our results demonstrate that ventricular FHF2 is highly phosphorylated, implicate differential roles for FHF2 in regulating neonatal and adult mouse ventricular NaV1.5, and suggest that the regulation of NaV1.5 by FHF2 phosphorylation is highly complex. eTOC Summary Lesage et al. identify the phosphorylation sites of FHF2 from mouse left ventricular NaV1.5 channel complexes. While no roles for FHF2 phosphosites could be recognized yet, the findings demonstrate differential FHF2-dependent regulation of neonatal and adult mouse ventricular NaV1.5 channels.
Understanding the Free Energy Landscape of Phase Separation in Lipid Bilayers using Molecular Dynamics

Liquid-liquid phase separation (LLPS) inside the cell often results in biological condensates that can critically impact cell homeostasis. Such phase separation events occur in multiple parts of cells, including the cell membranes, where the so-called “lipid raft” hypothesis posits the formation of ordered domains floating in a sea of disordered lipids. The resulting lipid domains often have functional roles. However, the thermodynamics of lipid phase separation and their resulting mechanistic effects on cell function and dysfunction are poorly understood. Understanding such complex phenomena in cell membranes, with their diverse lipid compositions, is exceptionally difficult. For this reasons, simple model systems that can recapitulate similar behavior are widely used to study this phenomenon. Despite these simplifications, the timescale and and length scales of domain formation pose a challenge for molecular dynamics (MD) simulations. Thus, most MD studies focus on spontaneous lipid phase separation — essentially measuring the sign (but not the amplitude) of the free energy change upon separation — rather than directly interrogating the thermodynamics. Here, we propose a proof-of-concept pipeline that can directly measure this free energy by combining coarse-grained MD with enhanced sampling protocols using a novel collective variable. This approach will be a useful tool to help connect the thermodynamics of phase separation with the mechanistic insights already available from molecular dynamics simulations. SIGNIFICANCE Standard molecular dynamics simulations can determine the sign the free energy change upon phase separation, but not the amplitude. We present a new method to determine the phase separation free energy for lipid membranes, based on a enhanced sampling using the weighted ensemble method combined with a novel collective variable, validated using coarse-grained simulations applied to several simple systems. The new method will be valuable as a way to develop models that connect molecular-level structural features to the thermodynamics of phase separation.
A synthetic signalling network imitating the action of immune cells in response to bacterial metabolism

State-of-the-art bottom-up synthetic biology allows us to replicate many basic biological functions in artificial cell-like devices. To mimic more complex behaviours, however, artificial cells would need to perform many of these functions in a synergistic and coordinated fashion, which remains elusive. Here we considered a sophisticated biological response, namely the capture and deactivation of pathogens by neutrophil immune cells, through the process of netosis. We designed a consortium consisting of two synthetic agents – responsive DNA-based particles and antibiotic-loaded lipid vesicles – whose coordinated action mimics the sought immune-like response when triggered by bacterial metabolism. The artificial netosis-like response emerges from a series of interlinked sensing and communication pathways between the live and synthetic agents, and translates into both physical and chemical antimicrobial actions, namely bacteria immobilisation and exposure to antibiotics. Our results demonstrate how advanced life-like responses can be prescribed with a relatively small number of synthetic molecular components, and outlines a new strategy for artificial-cell-based antimicrobial solutions.
The role of cuticular hydrocarbons in intraspecific aggression in the invasive ant Cardiocondyla obscurior

Cuticular hydrocarbons (CHCs) are important cues for nestmate discrimination and intraspecific aggression in ants. In invasive ants, diminished CHC profile diversity is suspected to contribute to the ecological and evolutionary success of populations by reducing intraspecific aggression between colonies. The ant Cardiocondyla obscurior has successfully colonized habitats around the world, reaching high local population densities. However, despite being invasive, colonies still react aggressively against each other, especially in interactions with non-nestmate alate queens. Here, we study whether CHCs are relevant for antagonistic interactions in this species, by combining behavioral experiments with gas-chromatography coupled with mass spectrometry (GC-MS). We show that queen and worker CHC profiles show pronounced quantitative as well as qualitative differences, that queens with depleted CHC profiles receive virtually no aggression from non-nestmates, and that aggression levels are positively correlated with the naturally occurring CHC profile differences between colonies. These findings provide first empirical evidence for a role of CHCs and chemical diversity in antagonistic behaviors against foreign queens in this species. They further suggest that invasive populations of C. obscurior are multicolonial and polydomous.
LCP1 Regulates Cell Motility in Chondrosarcoma and Correlates with Metastatic Potential and Poor Patient Outcomes

Chondrosarcoma (CSA) is the second most common primary malignancy of bone, whose aggressive potential and chemo-resistant nature result in extremely poor outcomes in patients with advanced disease. Grading and prognostication of these tumors remain a significant challenge for pathologists, and medical oncologists have no effective therapies to prevent or treat metastatic disease. In the present study, we sought to explore the pathogenesis and aggressive progression of chondrosarcoma by comparing gene expression differences from metastasizing and non-metastasizing CSA tumors. We hypothesized that metastasizing tumors have inherent differences that may be attributed to the dysregulation of specific oncogenic cell signaling pathways. RNA-Seq analysis from patient-derived low-passage cell lines of metastasizing and non-metastasizing tumors pinpointed the gene LCP1 (lymphocyte cytosolic protein 1) as upregulated in CSA cells from metastasizing tumors. Analysis of a large clinical cohort of CSA demonstrated that increased expression of LCP1 correlated with poor patient survival. In vitro analyses confirmed the ability of LCP1 to promote migration and invasion of CSA cells. These data support the key role of LCP1 on metastatic potential and poor prognosis in CSA. In conclusion, we confirm the ability of LCP1 to drive metastatic behavior and correlate with poor outcomes in patients.
Aberrant light sensing and motility in the green alga Chlamydomonas priscuii from the ice-covered Antarctic Lake Bonney

The Antarctic green alga Chlamydomonas priscuii is an obligate psychrophile and an emerging model for photosynthetic adaptation to extreme conditions. Endemic to the ice-covered Lake Bonney, this alga thrives at highly unusual light conditions characterized by very low light irradiance (<15 μmol m-2 s-1), a narrow wavelength spectrum enriched in blue light, and an extreme photoperiod. Genome sequencing of C. priscuii exposed an unusually large genome, with hundreds of highly similar gene duplicates and expanded gene families, some of which could be aiding its survival in extreme conditions. In contrast to the described expansion in the genetic repertoire in C. priscuii, here we suggest that the gene family encoding for photoreceptors is reduced when compared to related green algae. This alga also possesses a very small eyespot and exhibits an aberrant phototactic response, compared to the model Chlamydomonas reinhardtii. We also investigated the genome and behaviour of the closely related psychrophilic alga Chlamydomonas sp. ICE-MDV, that is found throughout the photic zone of Lake Bonney and is naturally exposed to higher light levels. Our analyses revealed a photoreceptor gene family and a robust phototactic response similar to those in the model Chlamydomonas reinhardtii. These results suggest that the aberrant phototactic response in C. priscuii is a result of life under extreme shading rather than a common feature of all psychrophilic algae. We discuss the implications of these results on the evolution and survival of shade adapted polar algae.
Discovery of NRG1-VII: a novel myeloid-derived class of NRG1 isoforms

18 19 Macrophages are a primary source of the growth factor Neuregulin-1 (NRG1), which has pleiotropic roles 20 in proliferation and differentiation of the stem cell niche in different tissues, and has been implicated in gut, 21 brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have 22 been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote the start 23 of this isoform class from a myeloid-specific transcriptional start site (TSS). Long-read sequencing identified 24 up to nine different NRG1-VII transcripts that show major structural differences from one another due to 25 use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in human 26 monocytes and tissue resident macrophages. Isoform switching via cassette exon usage and alternate 27 polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII
An Empirical Study on the Motivation of Helping Behavior in Rats

Using rodent models to explore the motivation of helping behaviors has become a new trend in recent years. Empathy, the alleviation of personal distress, and desire for social contact have been considered motivations for rodents to engage in helping behaviors. We used 108 Sprague-Dawley rats as subjects and modified the two-chambered helping behavior experimental setup in Carvalheiro and colleagues’ study to explore the main motivations of helping behavior in rodents through three experiments. The findings suggest that (1) the desire for social contact and pursuit of an interesting environment are the primary motivations for helping behavior, regardless of the presence of a dark chamber, and (2) the alleviation of personal distress and prior experience of social contact rather than distress experience contribute to the onset and persistence of helping behavior.
RTCpredictor: Identification of Read-Through Chimeric RNAs from RNA Sequencing Data

Read-through chimeric RNAs are gaining attention in cancer and other research fields, yet current tools often fail in predicting them. We have thus developed the first read-through chimeric RNA specific prediction method, RTCpredictor, utilizing a fast ripgrep algorithm to search for all possible exon-exon combinations of parental gene pairs. Compared with other ten popular tools, RTCpredictor achieved top performance on both simulated and real datasets. We randomly selected up to 30 candidate read-through chimeras predicted from each software method and experimentally validated a total of 109 read-throughs and on this set, RTCpredictor outperformed all the other methods. In addition, RTCpredictor (https://github.com/sandybioteck/RTCpredictor) has less memory requirements and faster execution time.
The Master Database of All Possible RNA Sequences and Its Integration with RNAcmap for RNA Homology Search

Recent success of AlphaFold2 in protein structure prediction relied heavily on co-evolutionary information derived from homologous protein sequences found in the huge, integrated database of protein sequences (Big Fantastic Database). In contrast, the existing nucleotide databases were not consolidated to facilitate wider and deeper homology search. Here, we built a comprehensive database by including the noncoding RNA sequences from RNAcentral, the transcriptome assembly and metagenome assembly from MG-RAST, the genomic sequences from Genome Warehouse (GWH), and the genomic sequences from MGnify, in addition to NCBI’s nucleotide database (nt) and its subsets. The resulting MARS database (Master database of All possible RNA sequences) is 20-fold larger than NCBI’s nt database or 60-fold larger than RNAcentral. The new dataset along with a new split-search strategy allows a substantial improvement in homology search over existing state-of-the-art techniques. It also yields more accurate and more sensitive multiple sequence alignments (MSA) than manually curated MSAs from Rfam for the majority of structured RNAs mapped to Rfam. The results indicate that MARS coupled with the fully automatic homology search tool RNAcmap will be useful for improved structural and functional inference of noncoding RNAs.
Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases

Background and objective For patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions. Methods In this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS). Results For the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan–Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided P<0.0001 for survival analysis). Conclusions This study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.
Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD

Background Previous research has demonstrated that epigenetic changes in specific hypothalamic-pituitary-adrenal (HPA) genes may predict successful psychotherapy in post-traumatic stress disorder (PTSD). A recent Phase 3 clinical trial reported high efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treating patients with severe PTSD compared to a therapy with placebo group (NCT03537014). This raises important questions regarding potential mechanisms of MDMA-assisted therapy. In the present study, we examined epigenetic changes in three key HPA axis genes before and after MDMA and placebo with therapy. As a pilot sub-study to the parent clinical trial, we assessed potential HPA epigenetic predictors for treatment response with genomic DNA derived from saliva (MDMA, n = 16; placebo, n = 7). Methylation levels at all 259 CpG sites annotated to three HPA genes (CRHR1, FKBP5, and NR3C1) were assessed in relation to treatment response as measured by the Clinician-Administered PTSD Scale (CAPS-5; Total Severity Score). Second, group (MDMA vs. placebo) differences in methylation change were assessed for sites that predicted treatment response. Results Methylation change across groups significantly predicted symptom reduction on 37 of 259 CpG sites tested, with two sites surviving false discovery rate (FDR) correction. Further, the MDMA-treatment group showed more methylation change compared to placebo on one site of the NR3C1 gene. Conclusion The findings of this study suggest that therapy-related PTSD symptom improvements may be related to DNA methylation changes in HPA genes and such changes may be greater in those receiving MDMA-assisted therapy. These findings can be used to generate hypothesis driven analyses for future studies with larger cohorts.
Antarctic Ardley Island terrace — An ideal place to study the marine to terrestrial succession of microbial communities

The study of chronosequences is an effective tool to study the effects of environmental changes or disturbances on microbial community structures, diversity, and the functional properties of ecosystems. Here, we conduct a chronosequence study on the Ardley Island coastal terrace of the Fildes Peninsula, Maritime Antarctica. The results revealed that prokaryotic microorganism communities changed orderly among the six successional stages. Some marine microbial groups could still be found in near-coastal soils of the late stage (lowest stratum). Animal pathogenic bacteria and stress-resistant microorganisms occurred at the greatest level with the longest succession period. The main driving factors for the succession of bacteria, archaea, and fungi along Ardley Island terrace were found through Adonis analysis (PERMANOVA). During analysis, soil elements Mg, Si, and Na were related to the bacterial and archaeal community structure discrepancies, while Al, Ti, K, and Cl were related to the fungal community structure discrepancies. On the other hand, other environmental factors also play an important role in the succession of microbial communities, which could be different among each microorganism. The succession of bacterial communities is greatly affected by pH and water content; archaeal communities are greatly affected by NH4+; fungal communities are affected by nutrients such as NO3−. In the analysis of the characteristic microorganisms along terrace, the succession of microorganisms was found to be influenced by complex and comprehensive factors. For instance, environmental instability, relationship with plants and ecological niches, and environmental tolerance. The results found that budding reproduction and/or with filamentous appendages bacteria were enriched in the late stage, which might be connected to its tolerance to rapid changes and barren environments. In addition, the decline in ammonia oxidation capacity of Thaumarchaeota archaeade with succession and the evolution of the fungi-plant relationship throughout classes were revealed. Overall, this research improves the understanding of the effect of the marine–to–terrestrial transition of the Ardley Island terrace on microbial communities. These findings will lay the foundation for more in-depth research regarding microbial adaptations and evolutionary mechanisms throughout the marine–terrestrial transition in the future.