Miracle-dz/UniFAR-FTUs huggingface dataset:
O-GlcNAcylation reduces phase separation and aggregation of the EWS N-terminal low complexity region

Many membraneless organelles are thought to be biomolecular condensates formed by phase separation of proteins and other biopolymers. Post-translational modifications (PTMs) can impact protein phase separation behavior, although for many PTMs this aspect of their function is unknown. O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is an abundant form of intracellular glycosylation whose roles in regulating biomolecular condensate assembly and dynamics have not been delineated. Using an in vitro approach, we found that O-GlcNAcylation reduces the phase separation propensity of the EWS N-terminal low complexity region (LCRN) under different conditions, including in the presence of the arginine-and glycine-rich RNA-binding domains (RBD). O-GlcNAcylation enhances fluorescence recovery after photobleaching (FRAP) within EWS LCRN condensates and causes the droplets to exhibit more liquid-like relaxation following fusion. Following extended incubation times, EWS LCRN+RBD condensates exhibit diminished FRAP, indicating a loss of fluidity, while condensates containing the O-GlcNAcylated LCRN do not. In HeLa cells, EWS is less O-GlcNAcylated following OGT knockdown and more prone to aggregation based on a filter retardation assay. Relative to the human proteome, O-GlcNAcylated proteins are enriched with regions that are predicted to phase separate, suggesting a general role of O-GlcNAcylation in regulation of biomolecular condensates. Insert Table of Contents artwork here For Table of Contents only.
Identification of Mutator-Derived Alternative Splicing Signatures of Genomic Instability for Improving the Clinical Outcome of Cholangiocarcinoma

Background Cholangiocarcinoma is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Genomic instability and alternative splicing (AS) events are hallmarks of carcinoma development and progression. The relationship between genomic instability, AS events, and tumor immune microenvironment remain unclear. Methods The splicing profiles of patients with cholangiocarcinoma were obtained from The Cancer Genome Atlas (TCGA) spliceSeq database. The transcriptomics, simple nucleotide variation (SNP) and clinical data of patients with cholangiocarcinoma were obtained from TCGA database. Patients were divided into genomic unstable (GU-like) and genomic stable (GS-like) groups according to their somatic mutations. Survival-related differential AS events were identified through integrated analysis of splicing profiling and clinical data. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was used to identify AS events occurring in genes enriched in cancer pathways. Pearson correlation was applied to analyze the splicing factors regulating AS events. CIBERSORT was used identify differentially infiltrating immune cells. Results A prognostic signature was constructed with six AS events. Using this signature, the hazard ratio of risk score for overall survival is 2.362. For TCGA patients with cholangiocarcinoma, the area under the receiver operating characteristic curve is 0.981. CDK11A is a negative regulator of survival associated AS events. Additionally, the CD8+ T cell proportion and PD-L1 expression are upregulated in patients with cholangiocarcinoma and high splicing signatures. Conclusion We provide a prognostic signature for cholangiocarcinoma overall survival. The CDK11A splicing factor and SLC46A1-39899-ES and IARS-86836-ES AS events may be potential targets for cholangiocarcinoma therapy. Patients with high AS risk score may be more sensitive to anti-PD-L1/PD1 immunotherapy.
Surfactin Facilitates Horizontal Gene Transfer in Bacillus subtilis

Genetic competence for the uptake and integration of extracellular DNA is a key process in horizontal gene transfer (HGT), one of the most powerful forces driving the evolution of bacteria. In several species, development of genetic competence is coupled with cell lysis. Using Bacillus subtilis as a model bacterium, we studied the role of surfactin, a powerful biosurfactant and antimicrobial lipopeptide, in genetic transformation. We showed that surfactin itself promotes cell lysis and DNA release, thereby promoting HGT. These results, therefore, provide evidence for a fundamental mechanism involved in HGT and significantly increase our understanding of the spreading of antibiotic resistance genes and diversification of microbial communities in the environment.
Amino Acid δ15N Can Detect Diet Effects on Pollution Risks for Yellow-Legged Gulls Overlooked by Trophic Position

The use of top-consumers as bioindicators of the health of food webs is hampered by uncertainties in their effective use of resources. In this study, the abundance of stable nitrogen isotopes in amino acids from homogenised eggs of the Yellow-legged Gull (Larus michahellis) allowed to identify variations in trophic resource exploitation between geographically adjacent nesting colonies in the Ria de Vigo (NW Spain) that exhibited marked differences in pollutants. Eggs from nests in the Cíes Islands (located in a National Park) showed a large variability in stable carbon and nitrogen isotopes in bulk egg content encompassing that of eggs from Vigo city (a major fishing harbour). However, both colonies differed in the relative concentration and abundance of nitrogen isotopes of lysine, an essential amino acid present in marine prey, but also extensively used in feed stocks for poultry and swine. Notwithstanding the similarity in trophic position for both colonies, gulls from Cíes Islands may have acquired a substantial fraction of lysine from garbage dump sites, while those of the urban colony relied on fish discards. This unexpected conclusion is partly supported by the large variability reported for gull’s diet in this region and calls for detailed estimations of diet when assessing the conservation status and pollution risks of marine ecosystems.
Extensins: Self-Assembly, Crosslinking, and the Role of Peroxidases

The extensin (EXT) network is elaborated by the covalent intermolecular crosslinking of EXT glycoprotein monomers, and its proper assembly is important for numerous aspects of basic wall architecture and cellular defense. In this review, we discuss new advances in the secretion of EXT monomers and the molecular drivers of EXT network self-assembly. Many of the functions of EXTs are conferred through covalent crosslinking into the wall, so we also discuss the different types of known intermolecular crosslinks, the enzymes that are involved, as well as the potential for additional crosslinks that are yet to be identified. EXTs also function in wall architecture independent of crosslinking status, and therefore, we explore the role of non-crosslinking EXTs. As EXT crosslinking is upregulated in response to wounding and pathogen infection, we discuss a potential regulatory mechanism to control covalent crosslinking and its relationship to the subcellular localization of the crosslinking enzymes.
The Impact of a Dedicated “Hot List” on the In-Patient Management of Patients With Acute Gallstone-Related Disease

Background: Index admission laparoscopic cholecystectomy is the standard of care for patients admitted to hospital with symptomatic acute cholecystitis. The same standard applies to patients suffering with mild acute biliary pancreatitis. Operating theatre capacity can be a significant constraint to same admission surgery. This study assesses the impact of dedicated theatre capacity provided by a specialist surgical team on rates of index admission cholecystectomy. Methods: This clinical cohort study compares the management of patients with symptomatic gallstone disease admitted to a tertiary care university teaching hospital over two equal but chronologically separate time periods. The periods were before and after service reconfiguration including a specialist HPB service with dedicated operating theatre time allocation. Results: There was a significant difference in the number of admissions over the two time periods with a greater proportion of patients having index admission surgery in the second time period with correspondingly fewer having more than one admission during this latter time period. In the second time period 43% of patients underwent index admission cholecystectomy compared to 23% in the first (P < 0.001). The duration of surgery was shorter for patients undergoing surgery during the second time period [135 (102–178) min in the first period and in the second period 106 (89–145) min] (P = 0.02). Discussion: This paper shows that the concentration of theatre resources and surgical expertise into regular theatre access for patients undergoing urgent laparoscopic cholecystectomy is an effective and safe model for dealing with acute biliary disease.
Sepsis—Pathophysiology and Therapeutic Concepts

Sepsis is a life-threatening condition and a global disease burden. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle.
Prefrontal Cortex Activation During Motor Sequence Learning Under Interleaved and Repetitive Practice: A Two-Channel Near-Infrared Spectroscopy Study

Training under high interference conditions through interleaved practice (IP) results in performance suppression during training but enhances long-term performance relative to repetitive practice (RP) involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent (BOLD) response using functional magnetic resonance imaging (fMRI) methodology resulting in mixed reports of prefrontal cortex (PFC) recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy (fNIRS) while discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance.
Low-Contrast High-Pass Visual Acuity Might Help to Detect Glaucoma Damage: A Structure-Function Analysis

Purpose: The conventional visual acuity (VA) test is not sensitive enough to detect glaucoma macular damage. We aimed to investigate whether VA measurements using low-contrast high-pass optotypes are more sensitive to macular dysfunction in glaucoma and to find the potential structural basis of this difference. Methods: A total of 147 subjects were recruited, including 118 patients with glaucoma (mean age: 46.08 ± 14.64 years) and 29 healthy controls (mean age: 39.83 ± 9.81 years). For each participant, monocular best-corrected VA was measured using a conventional chart and six high-pass charts at 100, 50, 10, 5, 2.5, and 1.25% contrast levels, respectively. The macular retinal thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness of all the glaucoma patients were obtained by spectral-domain optical coherence tomography (SD-OCT). Results: Compared with healthy subjects, glaucoma patients with normal vision demonstrated worse VAs in high-pass acuity measurements (0.22–0.93 vs. 0.28–1.08, p < 0.05). Receiver operating characteristic curve (ROC) showed that 1.25% low-contrast high-pass VA was optimal for discriminating between the controls and glaucoma patients (AUC: 0.918, p < 0.001; sensitivity: 77.33%; specificity: 96.55%). Compared with conventional VA, 1.25% high-pass VA correlated better with nasal-side macular retinal ganglion cell (RGC)-related parameters (r = −0.419 to −0.446 vs. r = −0.538 to −0.582; Fisher's Z transformation, pz < 0.05). There was no difference in the strength of correlations between the VAs measured using different charts and cpRNFL thickness (Fisher's Z transformation; pz > 0.05). Conclusions: VA measurement taken with low-contrast (1.25%) high-pass acuity chart is more sensitive in detecting central visual loss in glaucoma than that taken with the conventional chart. Macular RGC damage appears to be associated with low-contrast (1.25%) high-pass visual loss in glaucomatous eyes.
The Airway Pathobiome in Complex Respiratory Diseases: A Perspective in Domestic Animals

Respiratory infections in domestic animals are a major issue for veterinary and livestock industry. Pathogens in the respiratory tract share their habitat with a myriad of commensal microorganisms. Increasing evidence points towards a respiratory pathobiome concept, integrating the dysbiotic bacterial communities, the host and the environment in a new understanding of respiratory disease etiology. During the infection, the airway microbiota likely regulates and is regulated by pathogens through diverse mechanisms, thereby acting either as a gatekeeper that provides resistance to pathogen colonization or enhancing their prevalence and bacterial co-infectivity, which often results in disease exacerbation. Insight into the complex interplay taking place in the respiratory tract between the pathogens, microbiota, the host and its environment during infection in domestic animals is a research field in its infancy in which most studies are focused on infections from enteric pathogens and gut microbiota. However, its understanding may improve pathogen control and reduce the severity of microbial-related diseases, including those with zoonotic potential.
Bacterial and Archaeal Communities in Polymetallic Nodules, Sediments, and Bottom Waters of the Abyssal Clarion-Clipperton Zone: Emerging Patterns and Future Monitoring Considerations

Bacteria and archaea are key contributors to deep-sea biogeochemical cycles and food webs. The disruptions these microbial communities may experience during and following polymetallic nodule mining in the Clarion-Clipperton Zone (CCZ) of the North Pacific Ocean could therefore have broad ecological effects. Our goals in this synthesis are to characterize the current understanding of biodiversity and biogeography of bacteria and archaea in the CCZ and to identify gaps in the baseline data and sampling approaches, prior to the onset of mining in the region. This is part of a large effort to compile biogeographic patterns in the CCZ, and to assess the representivity of no-mining Areas of Particular Environmental Interest, across a range of taxa. Here, we review published studies and an additional new dataset focused on 16S ribosomal RNA (rRNA) gene amplicon characterization of abyssal bacterial and archaeal communities, particularly focused on spatial patterns. Deep-sea habitats (nodules, sediments, and bottom seawater) each hosted significantly different microbial communities. An east-vs.-west CCZ regional distinction was present in nodule communities, although the magnitude was small and likely not detectable without a high-resolution analysis. Within habitats, spatial variability was driven by differences in relative abundances of taxa, rather than by abundant taxon turnover. Our results further support observations that nodules in the CCZ have distinct archaeal communities from those in more productive surrounding regions, with higher relative abundances of presumed chemolithoautotrophic Nitrosopumilaceae suggesting possible trophic effects of nodule removal. Collectively, these results indicate that bacteria and archaea in the CCZ display previously undetected, subtle, regional-scale biogeography. However, the currently available microbial community surveys are spatially limited and suffer from sampling and analytical differences that frequently confound inter-comparison; making definitive management decisions from such a limited dataset could be problematic. We suggest a number of future research priorities and sampling recommendations that may help to alleviate dataset incompatibilities and to address challenges posed by rapidly advancing DNA sequencing technology for monitoring bacterial and archaeal biodiversity in the CCZ. Most critically, we advocate for selection of a standardized 16S rRNA gene amplification approach for use in the anticipated large-scale, contractor-driven biodiversity monitoring in the region.
Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

The kidneys and heart share functions with the common goal of maintaining homeostasis. When kidney injury occurs, many compounds, the so-called “uremic retention solutes” or “uremic toxins,” accumulate in the circulation targeting other tissues. The accumulation of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and inorganic phosphate leads to a loss of a substantial number of body functions. Although the concept of uremic toxins is dated to the 1960s, the molecular mechanisms capable of leading to renal and cardiovascular injuries are not yet known. Besides, the greatest toxic effects appear to be induced by compounds that are difficult to remove by dialysis. Considering the close relationship between renal and cardiovascular functions, an understanding of the mechanisms involved in the production, clearance and overall impact of uremic toxins is extremely relevant for the understanding of pathologies of the cardiovascular system. Thus, the present study has as main focus to present an extensive review on the impact of uremic toxins in the cardiovascular system, bringing the state of the art on the subject as well as clinical implications related to patient’s therapy affected by chronic kidney disease, which represents high mortality of patients with cardiac comorbidities.
Calibrating 3D Scanner in the Coordinate System of Optical Tracker for Image-To-Patient Registration

Three-dimensional scanners have been widely applied in image-guided surgery (IGS) given its potential to solve the image-to-patient registration problem. How to perform a reliable calibration between a 3D scanner and an external tracker is especially important for these applications. This study proposes a novel method for calibrating the extrinsic parameters of a 3D scanner in the coordinate system of an optical tracker. We bound an optical marker to a 3D scanner and designed a specified 3D benchmark for calibration. We then proposed a two-step calibration method based on the pointset registration technique and nonlinear optimization algorithm to obtain the extrinsic matrix of the 3D scanner. We applied repeat scan registration error (RSRE) as the cost function in the optimization process. Subsequently, we evaluated the performance of the proposed method on a recaptured verification dataset through RSRE and Chamfer distance (CD). In comparison with the calibration method based on 2D checkerboard, the proposed method achieved a lower RSRE (1.73 mm vs. 2.10, 1.94, and 1.83 mm) and CD (2.83 mm vs. 3.98, 3.46, and 3.17 mm). We also constructed a surgical navigation system to further explore the application of the tracked 3D scanner in image-to-patient registration. We conducted a phantom study to verify the accuracy of the proposed method and analyze the relationship between the calibration accuracy and the target registration error (TRE). The proposed scanner-based image-to-patient registration method was also compared with the fiducial-based method, and TRE and operation time (OT) were used to evaluate the registration results. The proposed registration method achieved an improved registration efficiency (50.72 ± 6.04 vs. 212.97 ± 15.91 s in the head phantom study). Although the TRE of the proposed registration method met the clinical requirements, its accuracy was lower than that of the fiducial-based registration method (1.79 ± 0.17 mm vs. 0.92 ± 0.16 mm in the head phantom study). We summarized and analyzed the limitations of the scanner-based image-to-patient registration method and discussed its possible development.
Combined Stochastic and Deterministic Processes Drive Community Assembly of Anaerobic Microbiomes During Granule Flotation

Advances in null-model approaches have resulted in a deeper understanding of community assembly mechanisms for a variety of complex microbiomes. One under-explored application is assembly of communities from the built-environment, especially during process disturbances. Anaerobic digestion for biological wastewater treatment is often underpinned by retaining millions of active granular biofilm aggregates. Flotation of granules is a major problem, resulting in process failure. Anaerobic aggregates were sampled from three identical bioreactors treating dairy wastewater. Microbiome structure was analysed using qPCR and 16S rRNA gene amplicon sequencing from DNA and cDNA. A comprehensive null-model approach quantified assembly mechanisms of floating and settled communities. Significant differences in diversity were observed between floating and settled granules, in particular, we highlight the changing abundances of Methanosaeta and Lactococcus. Both stochastic and deterministic processes were important for community assembly. Homogeneous selection was the primary mechanism for all categories, but dispersal processes also contributed. The lottery model was used to identify clade-level competition driving community assembly. Lottery “winners” were identified with different winners between floating and settled groups. Some groups changed their winner status when flotation occurred. Spirochaetaceae, for example, was only a winner in settled biomass (cDNA-level) and lost its winner status during flotation. Alternatively, Arcobacter butzerli gained winner status during flotation. This analysis provides a deeper understanding of changes that occur during process instabilities and identified groups which may be washed out—an important consideration for process control.