bluuebunny/crossref_metadata_2025_split huggingface dataset:
Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia
Authors: Maschke Charlotte , O’Byrne Jordan , Colombo Michele Angelo , Boly Melanie , Gosseries Olivia , Laureys Steven , Rosanova Mario , Jerbi Karim , Blain-Moraes Stefanie 
Published: November 2023

1AbstractConsciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects’ PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness.2Significance StatementComplexity has long been of interest in consciousness science and had a fundamental impact on many of today’s theories of consciousness. The perturbational complexity index (PCI) uses the complexity of the brain’s response to cortical perturbations to quantify the presence of consciousness. We propose criticality as a unifying framework underlying maximal complexity and sensitivity to perturbation in the conscious brain. We demonstrate that criticality measures derived from resting-state electroencephalography can distinguish conscious from unconscious states, using propofol, xenon and ketamine anesthesia, and from these measures we were able to predict the PCI with a mean error below 7%. Our results support the hypothesis that critical brain dynamics are implicated in the emergence of consciousness and may provide new directions for the assessment of consciousness.
Neonicotinoids andVarroamites force the extending of longevity in a bee colony during overwintering to forget
Authors: Yamada Toshiro , Yamada Yasuhiro 
Published: November 2023

AbstractA mathematical model that can estimate the apparent longevity of bee-colony proposed by the authors to clarify that the longevity normally changes with seasons as follows: The longevity maintains almost constant from at 20 to 30 days from late spring to late autumn, thereafter, it continues to extend till late spring up to 160 to 200 days. Immediately after overwintering, the longevity is shortened almost vertically from one sixth to one tenth. Such normal seasonal changes in longevity are shown when a pesticide-free food is administered to the bee-colony and when pesticide-containing sugar syrup is. However, abnormal seasonal changes in longevity, which does not extend even if winter approaches, are shown for the bee-colony ingesting neonicotinoid-containing pollen and for the colony infested withVarroamites.Judging from the fact that pollen is the main food for the bee-brood, that mites parasitize larvae and pupae, and that the vital functions and organs of honeybees are created during the larval and pupal stages, it can be inferred that a neonicotinoid-containing pollen paste and parasitic mites cause serious damage to the bee ability to detect the arrival of winter. Such dysfunction in the larval and pupal stages probably interferes with extending the longevity of adult bees even as winter approaches.
Machine learning-based revelation of GABBR1 and IQGAP2 as candidate biomarkers of pulmonary arterial hypertension and their correlation with immune infiltration
Authors: Wang Bao , Cheng Ju , Li Zengyou , Peng Yanfeng 
Published: November 2023

AbstractPulmonary arterial hypertension (PAH) is a pulmonary vascular disease with complex pathogenesis, and its intrinsic molecular mechanisms remain unclear. The aim of this study was to screen gene expression data from PAH patients, identify possible diagnostic indicators of PAH and to investigate the role of immune cell infiltration in the progression of PAH.This study made use of the gene expression dataset of PAH patients from the GEO database. R software was used to identify differentially expressed genes and perform functional enrichment analysis. The SVM-RFE, LASSO and Random Forest algorithms were then used to screen for PAH hub genes and validated in the peripheral blood and lung tissue datasets. Finally, the CIBERSORT algorithm was used to assess PAH lung tissue immune cell infiltration and to investigate the correlation between hub genes and immune cells.A total of 132 DEGs were screened in this study, which were centrally involved in the neuroreceptor-ligand activity pathway and associated with neurotransmission and hemoglobin complex. A total of 2 pivotal genes, GABBR1 and IQGAP2, were obtained by machine learning algorithms. The 2 pivotal genes had good predictive power as verified by ROC curves. Further immune infiltration analysis showed a decrease in T cells and an increase in the proportion of macrophages and dendritic cells in the lung tissue of PAH patients. The expression of GABBR1 was positively correlated with T cells and negatively correlated with macrophages and dendritic cells.In our study, we identified 2 potential diagnostic key genes: GABBR1 and IQGAP2. Our findings may provide a theoretical basis for the analysis of the underlying mechanisms of PAH and the development of targeted medicines.Highlight BoxKey findingsWe identified 2 potential key genes of PAH, GABBR1 and IQGAP2.What is known and what is new?Sympathetic hyperexcitability as well as immune responses are closely associated with the development of PAH, and pulmonary vascular hyperplasia is a key pathogenetic mechanism of PAH.Important biomarkers related to neuroreceptors and immune responses in PAH lung tissue have not been identified, while our study identified GABBR1 as a key neuroreceptor and immune cell regulator in PAH. IQGAP2 could be a new hotspot direction for pulmonary vascular remodeling.What is the implication, and what should change now?GABBR1 and IQGAP2 may be potential therapeutic targets for PAH. The new horizon provided by this study will provide some reference for subsequent PAH studies.
A network-based methodology to reconstruct biodiversity based on interactions with indicator species
Authors: Bouderbala Ilhem , Fortin Daniel , Tremblay Junior A. , Allard Antoine , Desrosiers Patrick 
Published: November 2023

AbstractThe relationship between species presence, biodiversity reconstruction, and latitudinal gradients is a complex and multifaceted topic that has been the subject of extensive research in ecology. Recent studies have provided valuable insights into the patterns and drivers of these phenomena. Also, with the ongoing decline in biodiversity, there is a need for efficient field monitoring techniques. Indicator species (IS) emerged as a promising tool to monitor diversity because their presence indicates a maximum number of conditionally co-occurring species. We aim to assess the effectiveness of IS for biodiversity reconstruction implicitly based on their co-occurrence with other species through a network-based methodology. The IS are identified based on various network metrics and the likelihood of species’ occurrences is computed based on (1) their conditional occurrence probability with IS and (2) the occurrence probability of IS. We test the approach with field observations of birds in the Côte-Nord region of Québec. From our methodology, the climate latitudinal gradient plays a significant role on the alternation in composition of IS with an almost complete turnover between northern and southern networks. The latitudinal gradient impacts also the nature of the inter-specific interactions with more avoidance relationship toward the Tropics and more cooperation liaisons toward the north. Regarding the effectiveness in the reconstruction of assemblages occurrence, we observe a strong negative correlation (r ≤ −0.95) between the percentage of sites occupied and the dissimilarity between the original and the estimated occurrences. More precisely, species must be present in more than 29% and 33% of northern and southern sites to recover well from its co-occurrence with IS. Therefore, it is more challenging to reconstruct biodiversity in communities closet to Tropics due to higher complex interactions and interspecific competition in these areas, which make it more difficult to infer community composition. In conclusion, our method demonstrates that it is possible to predict local species assemblages based on their implicit interactions with local IS. Nevertheless, the relatively low success of less present species illustrates the need for further theoretical development to reconstruct biodiversity, mainly to recover the occurrence of rare species.
Coenzyme-Protein Interactions since Early Life
Authors: Sanchez-Rocha Alma Carolina , Makarov Mikhail , Pravda Lukáš , Novotný Marian , Hlouchová Klára 
Published: November 2023

AbstractRecent findings in protein evolution and peptide prebiotic plausibility have been setting the stage for reconsidering the role of peptides in the early stages of life’s origin. Ancient protein families have been found to share common themes and proteins reduced in composition to prebiotically plausible amino acids have been reported capable of structure formation and key functions, such as binding to RNA. While this may suggest peptide relevance in early life, their functional repertoire when composed of a limited number of early residues (missing some of the most sophisticated functional groups of today’s alphabet) has been debated.Cofactors enrich the functional scope of about half of extant enzymes but whether they could also bind to peptides lacking the evolutionary late amino acids remains speculative. The aim of this study was to resolve the early peptide propensity to bind organic cofactors by analysis of protein-coenzyme interactions across the Protein Data Bank (PDB). We find that the prebiotically plausible amino acids are more abundant in the binding sites of the most ancient coenzymes and that such interactions rely more frequently on the involvement of the protein backbone atoms and metal ion cofactors. Moreover, we have identified a few select examples in today’s enzymes where coenzyme binding is supported solely by prebiotically available amino acids. These results imply the plausibility of a coenzyme-peptide functional collaboration preceding the establishment of the Central Dogma and full protein alphabet evolution.
Sequence-ensemble-function relationships for disordered proteins in live cells
Authors: Emenecker Ryan J. , Guadalupe Karina , Shamoon Nora M. , Sukenik Shahar , Holehouse Alex S. 
Published: November 2023

ABSTRACTIntrinsically disordered protein regions (IDRs) are ubiquitous across all kingdoms of life and play a variety of essential cellular roles. IDRs exist in a collection of structurally distinct conformers known as an ensemble. An IDR’s amino acid sequence determines its ensemble, which in turn can play an important role in dictating molecular function. Yet a clear link connecting IDR sequence, its ensemble properties, and its molecular function in living cells has not been directly established. Here, we set out to test this sequence-ensemble-function paradigm using a novel computational method (GOOSE) that enables the rational design of libraries of IDRs by systematically varying specific sequence properties. Using ensemble FRET, we measured the ensemble dimensions of a library of rationally designed IDRs in human-derived cell lines, revealing how IDR sequence influences ensemble dimensionsin situ.Furthermore, we show that the interplay between sequence and ensemble can tune an IDR’s ability to sense changes in cell volume - ade novomolecular function for these synthetic sequences. Our results establish biophysical rules for intracellular sequence-ensemble relationships, enable a new route for understanding how IDR sequences map to function in live cells, and set the ground for the design of synthetic IDRs withde novofunction.
Combined Bioinformatic and Splicing Analysis of Likely Benign Intronic and Synonymous Variants Reveals Evidence for Pathogenicity
Authors: Hirschi Owen R. , Felker Stephanie A. , Rednam Surya P. , Vallance Kelly L. , Williams Parsons D. , Roy Angshumoy , Cooper Gregory M. , Plon Sharon E. 
Published: November 2023

AbstractBackgroundCurrent clinical variant analysis pipelines focus on coding variants and intronic variants within 10-20 bases of an exon-intron boundary that may affect splicing. The impact of newer splicing prediction algorithms combined within vitrosplicing assays on rare variants currently considered Benign/Likely Benign (B/LB) is unknown.MethodsExome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.20), and scored as potentially deleterious by CADD (>10.0). Total cellular RNA was extracted from monocytes and RT-PCR products analyzed. Subsequently, rare synonymous or intronic B/LB variants in a subset of genes submitted to ClinVar were similarly evaluated. Variants predicted to lead to a frameshifted splicing product were functionally assessed using anin vitrosplicing reporter assay in HEK-293T cells.ResultsKidsCanSeq exome data analysis revealed a rare, heterozygous, intronic variant (NM_177438.3(DICER1):c.574-26A>G) predicted by SpliceAI to result in gain of a secondary splice acceptor site. The proband had a personal and family history of pleuropulmonary blastoma consistent withDICER1syndrome but negative clinical sequencing reports. Proband RNA analysis revealed alternativeDICER1transcripts including the SpliceAI-predicted transcript.Similar bioinformatic analysis of synonymous or intronic B/LB variants (n=31,715) in ClinVar from 61 Mendelian disease genes yielded 18 variants, none of which could be scored by MaxEntScan. Eight of these variants were assessed (DICER1n=4,CDH1n=2,PALB2n=2) usingin vitrosplice reporter assay and demonstrated abnormal splice products (mean 66%; range 6% to 100%). Available phenotypic information from submitting laboratories demonstratedDICER1phenotypes in 2 families (1 variant) and breast cancer phenotypes forPALB2in 3 families (2 variants).ConclusionsOur results demonstrate the power of newer predictive splicing algorithms to highlight rare variants previously considered B/LB in patients with features of hereditary conditions. Incorporation of SpliceAI annotation of existing variant data combined with either direct RNA analysis orin vitroassays has the potential to identify disease-associated variants in patients without a molecular diagnosis.
The WD Domain OfAtg16l1Crucial For LC3-Associated Phagocytosis Is Not Required For Preserving Skin Homeostasis In Mice
Authors: Conway Shannon , Jefferson Matthew , Warren Derek T. , Wileman Thomas , Morris Christopher J. 
Published: November 2023

ABSTRACTThe skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as an initial safeguard against foreign and harmful environmental and biological factors. The barrier function is governed by the epidermis, a stratified epithelium composed of an outermost cornified envelope, several differentiated layers, and an innermost basal layer, anchored to the basement membrane (BM). Below the BM lies the dermis, which is composed of an extracellular matrix (ECM), formed by the dermal fibroblasts and dermal adipose tissue. The skin is subject to constant cellular turnover (terminal differentiation) that maintains the homeostatic state of the skin. Recently, autophagy has been implicated in epidermal differentiation and in preserving homeostasis in the skin. The AKT/mTORC1 pathway is a key regulator for epidermal development and differentiation, and conditions (e.g., psoriasis) are linked to the hyperactivation of these key autophagy regulators. A further process known as LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 E230 mouse model (E230), deficient for LAP, has been widely used to study the effects of LAP-deficiency and autophagy in tissue homeostasis.Here, the E230 model was used to study the relationship between skin homeostasis and LAP and to determine whether LAP-deficient mice (WD) display a cutaneous skin phenotype. Histological analysis of male 1-year-old Wild Type (WT) and WD mice skin revealed morphological differences in dorsal and tail skin. qPCR analysis of key keratins showed no differences (p > 0.05) when compared between genotypes. This was confirmed by western blotting studies. In addition, the expression of general proliferation markers (Akt & ERK2) showed a small reduction (p < 0.05) in the WD mice skin. General skin barrier formation was assessed by dye permeation assays, which demonstrated full and proper formation of the skin barrier at E18.5 in both WT and WD. Notable dermal thinning in the WD mice skin (p < 0.0001), led us to examine the biomechanical properties to dismiss any abnormalities relating to biomechanical functionality. Results indicate that WT and WD mouse skin show identical biomechanical properties at these ages (p < 0.05 and p < 0.01, respectively). In summary, the noted differences in the dermal and epidermal histology of WD skin were shown to be functionally insignificant in terms of epidermal permeability and dermal biomechanics.
A Perturbation Approach for Refining Boolean Models of Cell Cycle Regulation
Authors: Banerjee Anand , Rahaman Asif Iqbal , Mehandale Alok , Kraikivski Pavel 
Published: November 2023

ABSTRACTConsiderable effort is required to build mathematical models of large protein regulatory networks. Utilizing computational algorithms that guide model development can significantly streamline the process and enhance the reliability of the resulting models. In this article we present a perturbation approach for developing data-centric Boolean models of cell cycle regulation. We assign a score to a network based on the steady states of the network-dynamics, and the dynamical trajectories corresponding to the initial conditions. Then, perturbation analysis is used to find new networks with lower scores, in which dynamical trajectories traverse through the correct cell cycle path with high frequency. We apply this method to refine Boolean models of cell cycle regulation in budding yeast and mammalian cells.
Exploring the local field potential signal from the subthalamic nucleus for phase-targeted auditory stimulation in Parkinson’s disease
Authors: Krugliakova Elena , Karpovich Artyom , Stieglitz Lennart , Huwiler Stephanie , Lustenberger Caroline , Imbach Lukas , Bujan Bartosz , Jedrysiak Piotr , Jacomet Maria , Baumann Christian R. , Fattinger Sara 
Published: November 2023

AbstractBackgroundEnhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, might offer therapeutic benefits for patients with Parkinson’s disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in the surface EEG signal in real-time.ObjectiveWe aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and evaluate the PTAS-related electrophysiologic changes.MethodsWe enrolled patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for the deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients participated in 3 full-night recordings, including one between-surgeries recording and two recordings during rehabilitation, one with DBS+ (on) and one with DBS-(off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions.ResultsOur results show that during NREM sleep, slow waves of the cortex and STN are time-locked. We observed the effects of PTAS in STN-LFP in all types of analyses, including spectral, coherence, and event-related potentials.ConclusionOur findings suggest that PTAS could be implemented using STN-LFP signal for slow wave detection. Additionally, we propose options for better STN-LFP signal preprocessing, including different referencing and filtering that could make the detection of the cortical slow waves in STN-LFP more reliable.