Miracle-dz/UniFAR-FTUs huggingface dataset:
Usefulness of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for the Management of Intrahepatic Bile Duct Lesions (with Videos)

Background/Aims Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusions Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients.
New insights from XRF core scanning data into boreal lake ontogeny during the Eemian (Marine Isotope Stage 5e) at Sokli, northeast Finland

Abstract Biological proxies from the Sokli Eemian (Marine Isotope Stage 5e) paleolake sequence from northeast Finland have previously shown that, unlike many postglacial records from boreal sites, the lake becomes increasingly eutrophic over time. Here, principal components (PC) were extracted from a high resolution multi-element XRF core scanning dataset to describe minerogenic input from the wider catchment (PC1), the input of S, Fe, Mn, and Ca-rich detrital material from the surrounding Sokli Carbonatite Massif (PC2), and chemical weathering (PC3). Minerogenic inputs to the lake were elevated early in the record and during two abrupt cooling events when soils and vegetation in the catchment were poor. Chemical weathering in the catchment generally increased over time, coinciding with higher air temperatures, catchment productivity, and the presence of acidic conifer species. Abiotic edaphic processes play a key role in lake ontogeny at this site stemming from the base cation- and nutrient-rich bedrock, which supports lake alkalinity and productivity. The climate history at this site, and its integrated effects on the lake system, appear to override development processes and alters its long-term trajectory.
Ultrastructural and glycoproteomic characterization of Prevotella intermedia: Insights into O‐glycosylation and outer membrane vesicles

Abstract Prevotella intermedia, a Gram‐negative bacterium from the Bacteroidota phylum, is associated with periodontitis. Other species within this phylum are known to possess the general O‐glycosylation system. The O‐glycoproteome has been characterized in several species, including Tannerella forsythia, Porphyromonas gingivalis, and Flavobacterium johnsoniae. In our study, we used electron cryotomography (cryoET) and glycoproteomics to reveal the ultrastructure of P. intermedia and characterize its O‐glycoproteome. Our cryoET analysis unveiled the ultrastructural details of the cell envelope and outer membrane vesicles (OMVs) of P. intermedia. We observed an electron‐dense surface layer surrounding both cells and OMVs. The OMVs were often large (>200 nm) and presented two types, with lumens being either electron‐dense or translucent. LC‐MS/MS analyses of P. intermedia fractions led to the identification of 1655 proteins, which included 62 predicted T9SS cargo proteins. Within the glycoproteome, we identified 443 unique O‐glycosylation sites within 224 glycoproteins. Interestingly, the O‐glycosylation motif exhibited a broader range than reported in other species, with O‐glycosylation found at D(S/T)(A/I/L/M/T/V/S/C/G/F/N/E/Q/D/P). We identified a single O‐glycan with a delta mass of 1531.48 Da. Its sequence was determined by MS2 and MS3 analyses using both collision‐induced dissociation and high‐energy collisional dissociation fragmentation modes. After partial deglycosylation with trifluoromethanesulfonic acid, the O‐glycan sequence was confirmed to be dHex‐dHex‐HexNAc (HPO3‐C6H12O5)‐dHex‐Hex‐HexA‐Hex(dHex). Bioinformatic analyses predicted the localization of O‐glycoproteins, with 73 periplasmic proteins, 53 inner membrane proteins, 52 lipoproteins, 26 outer membrane proteins, and 14 proteins secreted by the T9SS.
Mount Farinaccio rockfall: comparision between kinematic simulations and experimental field tests

Analisi del moto di caduta massi al Sasso Farinaccio (SO): confronto tra simulazioni cinematiche e sperimentazioni in sito.I fenomeni di caduta massi sono frequenti nelle aree alpine e, per mitigare i rischi che creano alla popolazione ed agli insediamenti umani, e indispensabile una corretta previsione delle possibili traiettorie e dei parametri cinematici del moto che i blocchi in incipienza di movimento assumerebbero qualora si staccassero dalla parete.Il presente contributo riguarda lo studio dettagliato del moto di caduta massi e della sua propagazione, ottenuto grazie alla realizzazione di prove sperimentali effettuate in Val Grosina (SO). I risultati della sperimentazione sono stati paragonati con quelli provenienti da simulazioni cinematiche precedentemente effettuate nell'area d'indagine, utilizzando differenti metodi, sia bidimensionali sia tridimensionali. In una prima serie di simulazioni i dati di input caratterizzanti il moto dei blocchi sono stati ipotizzati sulla base dei valori bibliografici, ottenuti in contesti geologici e geomorfologici simili a quello di indagine, mentre in una seconda serie tali valori sono stati stimati basandosi sulla posizione di arresto di alcuni blocchi crollati nell'area di studio nel 2010. Il confronto dei risultati ottenuti utilizzando i diversi approcci con quelli sperimentali, mostra che, per ottenere previsioni affidabili delle traiettorie dei blocchi e quindi mappe di pericolosita attendibili, e necessario effettuare un'accurata calibrazione dei parametri che caratterizzano il moto di caduta.
Short-chain fatty acids propionate and butyrate control growth and differentiation linked to cellular metabolism

The short-chain fatty acids (SCFA) propionate and butyrate are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. In order to better understand the function of these modifications we used ChIP-seq to map the genome-wide location of four short-chain acyl histone marks H3K18pr/bu and H4K12pr/bu in treated and untreated colorectal cancer (CRC) and normal cells, as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions along with gene expression to access the function of the target regions. Our data demonstrate that propionate and butyrate act as promoters of growth, differentiation as well as ion transport. We propose a mechanism involving direct modification of specific genomic regions, resulting in increased chromatin accessibility, and in case of butyrate, opposing effects on the proliferation of normal versus CRC cells.
The Compression Mating Fossil of Sciarid Fly (Diptera: Sciaridae) from Shiobara, Tochigi Prefecture, Japan

Abstract. Preservations illustrating insect reproductive behaviors are much rarer in compression fossils than in amber. We discovered a copulating compression fossil of the sciarid flies from the Pleistocene Shiobara Group, Tochigi Prefecture, Japan, which is briefly described herein. The specimen represents one of the rare examples of a compression fossil showing mating dipteran insects. This finding implies that the small bodies of sciarid flies which readily fall onto the water surface may have contributed to the preservation of our copulating fossil. Moreover, the depositional environment of the paleo-Shiobara Lake was the main factor that served to preserve this specimen.
The elephant and ivory trade in Thailand

Since 1997, TRAFFIC has been carrying out country surveys of trade in ivory and, in some cases, live elephants. In 2006/2007, TRAFFIC set out to compile existing and new information on the trade in elephants and elephant products in Thailand in consultation with relevant experts and stakeholders, including carvers, traders, retailers and government regulators. This study examines the legislative framework governing trade in elephants and elephant products, documenting the continuing availability of ivory products in key locations, and analyses the current situation in Thailand relative to the requirements under Resolution Conf. 10.10 (Rev. CoP14). The field work for this report was carried out in Bangkok, Chiang Mai and the Phayuha Kiri and Uthai Thani area south of Nakhon Sawan from 2 to 23 December 2006 and in Bangkok from 16 to 25 February 2007. A follow-up monitoring and assessment survey was carried out in the same areas from 14 January to 9 February 2008. TRAFFIC recorded the number and types of ivory items seen for sale and obtained a representative set of prices. The vendors were interviewed to ask them where they obtained the ivory, how well it was selling in order to assess turnover, who the main buyers were and if they knew where any ivory carving workshops were located. TRAFFIC then visited ivory craftsmen who could be located and interviewed them in an attempt to find out where they obtained their raw ivory, what prices they paid for different weight and type classes and where they sold their products. They were also asked if they exported their products anywhere or if they sold on the Internet.
The Impact of the AMOC Resumption in the Western South Atlantic Thermocline at the Onset of the Last Interglacial

After glacial terminations, large amounts of heat and salt were transferred from low to high latitudes, which is a crucial phenomenon for the reestablishment of the Atlantic Meridional Overturning Circulation (AMOC). However, how different glacial terminations evolved in the (sub)tropics is still poorly documented. Here we use foraminifera oxygen (δ18O) and carbon (δ13C) stable isotopes to show that the North Atlantic heat piracy, following the AMOC resumption at the early Last Interglacial, affected the thermocline δ18O levels of the subtropical western South Atlantic. Because of the cooling imposed by this process, glacial δ18O persisted in the thermocline for ~7 kyr after the onset of the Last Interglacial, dampening the effect of sea level rise usually imprinted on foraminifera δ18O during terminations. Faunal composition and δ13C also suggest the existence of a colder and thicker South Atlantic Central Water coeval with the AMOC recovery. This process apparently did not occur during the last deglaciation.
Laboratory application of the Aquascope approach of automated imaging and classification for long-term plankton monitoring

Anthropogenic changes such as climate change and pollution have strong effects on plankton and its ecosystem services. In freshwater, phytoplankton forms the basis of the food web and plays a key role in water quality. It is therefore important to monitor the plankton community. In Switzerland, lake plankton has been monitored for decades by cantonal authorities. But in the future, there will be a limitation in the availability of trained taxonomists that are able to count plankton samples under the microscope as well as time and budget constraints. New technologies will be needed to fulfil the federal requirements on the monitoring of lakes in the future. Here we focus on two such instruments, both based on plankton automated imaging: the FlowCam and the Aquascope. The first is a commercially available instrument, the second is custom made. They are the only automated imaging instruments that can track freshwater plankton across the desired size range (phytoplankton and zooplankton). Their design makes them the state of the art technologies to make quantitative observations of plankton. While the FlowCam is a laboratory instrument, the Aquascope is originally designed for field deployment. In this report, we focus the empirical work on the laboratory application of the Aquascope approach of automated imaging and classification for long term plankton monitoring. We find that there are major advantages of the Aquascope approach but the application as a laboratory instrument still needs further development. The major advantages of the Aquascope approach compared to traditional, human-supervised, microscopy methods are the automation and the speed of the data processing, the availability of individual level traits and the management of the data generated. One of the major drawbacks is the lack of taxonomic resolution (mostly at the genus level). Nevertheless, we show that with a larger benchmarking project, it might be possible to continue the long term time series on a coarse taxonomic level as usually reported by cantonal authorities to the general public. We discuss advantages and limitations of Aquascope relative to traditional microscopy and FlowCam, and propose ways forward for future development and application of this approach.
Concatenation of segmented viral genomes for reassortment analysis

Most reassortment identification methods are based on searching for phylogenetic discrepancies between phylogenetic trees for different segments. Other methods use pairwise genetic distances or compare the position of individual genome components in a tree relative to a reference component of the viral genome. However, such approaches are labour-intensive and hardly scalable. Recent advances in the availability of viral sequencing technologies have led to the sequencing of large numbers of pathogen genomes, making manual processing of this large data difficult. At the same time, recombination analysis methods can process almost any number of sequences simultaneously. Such approaches are not suitable for the simultaneous analysis of multiple segments and are therefore not used to search for reassortment events. However, in the case of sequential concatenation of all segments, the methods of recombination analysis can be used to detect traces of reassortment events. The code is available at https://github.com/melibrun/Concatenation-of-segmented-viral-genomes-for-reassortment-analysis. The service is implemented as a web application https://melibrun.shinyapps. io/viralsegmentconcatenator1/. It concatenates segmented viral genomes for reassortment analysis. The tool accepts files in GenBank format as input and generates a set of sequences in fasta format that are sequentially concatenated sequences of viral segments named in accordance with the “strain” field of the GenBank record annotation. In order to use recombination search algorithms in the study of reassortment events, we have developed a method (Virus Segment Concatenator, VSC) to automatically concatenate the sequences of all segments of a virus into a single sequence. The applicability of VSC for automated searches for reassortment events was demonstrated using CCHFV, an H5N5 subtype of influenza virus.
Arg18 substitutions reveal the capacity of the HIV-1 capsid protein for non-fullerene assembly

In the fullerene cone HIV-1 capsid, the central channels of the hexameric and pentameric capsomers each contain a ring of arginine (Arg18) residues that perform essential roles in capsid assembly and function. In both the hexamer and pentamer, the Arg18 rings coordinate inositol hexakisphosphate, an assembly and stability factor for the capsid. Previously, it was shown that amino-acid substitutions of Arg18 can promote pentamer incorporation into capsid-like particles (CLPs) that spontaneously assemble in vitro under high salt conditions. Here, we show that these Arg18 mutant CLPs contain a non-canonical pentamer conformation and distinct lattice characteristics that do not follow the fullerene geometry of retroviral capsids. The Arg18 mutant pentamers resemble the hexamer in intra-oligomeric contacts, and forms a unique tetramer-of-pentamers that allows for incorporation of an octahedral vertex with a cross-shaped opening in the hexagonal capsid lattice. Our findings highlight an unexpected degree of structural plasticity in HIV-1 capsid assembly.
Ilamycin E and ilamycin F are dual inhibitors of ClpX and ClpC1 in mycobacteria

The Clp protease system, which is crucial for maintaining protein homeostasis in mycobacteria, has become a promising target. Numerous non-ribosomal natural cyclic peptides, including ilamycins, have been reported to possess antitubercular activities by targeting the ClpC1 component of the ClpC1P1P2 proteasome. In this study, we found that ilamycin E and F (ILE/F) exhibit significantly more potent mycobactericidal activities than other ilamycin components by targeting both ClpX and ClpC1 components of the ClpC1P1P2 and ClpXP1P2 complexes. To our knowledge, this is the first report on the killing of mycobacteria by compounds through the targeting of ClpX. ILE/F have delayed antimicrobial activities and show synergistic or additive activities with many antituberculosis drugs against Mycobacterium tuberculosis, which is consistent with their mechanisms of action. Novel insertion mutations in clpC1, in addition to previously reported mutations, and a unique mutation in clpX have been identified and proven to cause resistance to ILE/F in mycobacteria. ILE markedly impedes the proteolytic function of the ClpC1P1P2 complex and may disrupt the function of the ClpXP1P2 complex by binding to ClpX. ILE/F are highly effective against mycobacteria by targeting both the ClpC1P1P2 and ClpXP1P2 complexes, highlighting the Clp complexes as promising potent targets, especially through a dual-targeting strategy.
Antibiotic Bacteria Interaction: Dataset and Benchmarking

This study introduces a dataset for drug-bacteria associations (DBA) that affects humans. Our contribution extends beyond merely curating the association matrix; we also conduct genomic similarity computations for all known bacteria impacting humans and assess structural similarities for all antibiotic drugs. This is a first of a kind dataset serving the fundamental goal of streamlining antibiotic repurposing for bacterial infections. We conducted thorough benchmarking on this dataset using state-of-the-art drug repurposing models. Furthermore, we applied this dataset to three case studies involving drug-resistant bacterial infections. Our results indicate that the dataset coupled with the algorithms are indeed effective for repurposing drugs with the potential for treating drug resistant bacterial infections.
Advancing Drug-Target Interactions Prediction: Leveraging a Large-Scale Dataset with a Rapid and Robust Chemogenomic Algorithm

Predicting drug-target interactions (DTIs) is crucial for drug discovery, and heavily relies on supervised learning techniques. Supervised learning algorithms for DTI prediction use known DTIs to learn associations between molecule and protein features, allowing for the prediction of new interactions based on learned patterns. In this paper, we present a novel approach addressing two key challenges in DTI prediction: the availability of large, high-quality training datasets and the scalability of prediction methods. First, we introduce LCIdb, a curated, large-sized dataset of DTIs, offering extensive coverage of both the molecule and druggable protein spaces. Notably, LCIdb contains a much higher number of molecules than traditional benchmarks, expanding coverage of the molecule space. Second, we propose Komet (Kronecker Optimized METhod), a DTI prediction pipeline designed for scalability without compromising performance. Komet leverages a three-step framework, incorporating efficient computation choices tailored for large datasets and involving the Nyström approximation. Specifically, Komet employs a Kronecker interaction module for (molecule, protein) pairs, which is sufficiently expressive and whose structure allows for reduced computational complexity. Our method is implemented in open-source software, leveraging GPU parallel computation for efficiency. We demonstrate the efficiency of our approach on various datasets, showing that Komet displays superior scalability and prediction performance compared to state-of-the-art deep learning approaches. Additionally, we illustrate the generalization properties of Komet by showing its ability to solve challenging scaffold-hopping problems gathered in the publicly available LH benchmark. Komet is available open source at https://komet.readthedocs. io and all datasets, including LCIdb, can be found at https://zenodo.org/records/10731713.
Differential cell type-specific function of the aryl hydrocarbon receptor and its repressor in diet-induced obesity and fibrosis

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor regulating xenobiotic responses as well as physiological metabolism. Dietary AhR ligands activate the AhR signaling axis in the intestine and throughout the organism, whereas AhR activation is negatively regulated by the AhR repressor (AhRR). While AhR-deficient mice are known to be resistant to diet-induced obesity (DIO), we here demonstrate that AhRR deficiency also leads to a robust, but not as profound protection from DIO and hepatosteatosis. Under conditions of DIO, AhRR-/- mice did not accumulate TCA cycle intermediates in the circulation in contrast to wild-type (WT) mice, indicating protection from metabolic dysfunction. This effect could be mimicked by dietary supplementation of AhR ligands in WT mice. Because of the predominant expression of the AhRR in myeloid cells, AhRR-deficient macrophages were analyzed for changes in metabolism and showed major metabolic alterations regarding oxidative phosphorylation and mitochondrial activity as well as increased expression of genes involved in de novo lipogenesis and mitochondrial biogenesis. Mice with a genetic deficiency of the AhRR in myeloid cells did not show alterations in weight gain after high fat diet (HFD) but demonstrated ameliorated liver damage compared to control mice. Further, deficiency of the AhR in myeloid cells also did not affect weight gain but led to enhanced liver damage and adipose tissue fibrosis compared to controls. Although conditional ablation of either the AhR or AhRR in myeloid cells did not recapitulate the phenotype of the global knockout, our findings suggest that enhanced AhR signaling in myeloid cells deficient for AhRR protects from diet-induced liver damage and fibrosis, whereas myeloid cell-specific AhR deficiency is detrimental.
The Origins of ATP Dependence in Biological Nitrogen Fixation

Life depends on a conserved set of chemical energy currencies that are relics of early biochemistry. One of these is ATP, a molecule that, when paired with a divalent metal ion such as Mg2+, can be hydrolyzed to support numerous cellular and molecular processes. Despite its centrality to extant biochemistry, it is unclear whether ATP supported the function of ancient enzymes. We investigate the evolutionary necessity of ATP by experimentally reconstructing an ancestral variant of the key N2-reducing enzyme nitrogenase. We show that the ancestor has a strict requirement for ATP and its hydrolysis is coupled to electron transfer for N2 reduction. Our results provide direct laboratory evidence of ATP usage by an ancient enzyme, and underscore how biomolecular constraints can entirely decouple cofactor selection from environmental availability.