julilili42/papers huggingface dataset:
Iron Chelation and Siderophores
2022-01-27

The great importance of iron in microbial metabolism can be rationalized in terms of its unique chemical and physicochemical properties. Iron has two oxidation states, ferrous and ferric, within the range of physiological reductants. This makes it suitable for the active site of a great number of enzymes with redox activity. Iron is the key element of the heme group in hemoglobin, myoglobin, cytochromes a3, b5, c, P-450, among others. It is contained in catalases, peroxidases, ribonucleotide reductase and various iron-sulfur-proteins. Useful redox activity is well exemplified by the monooxygenase mediated oxidative metabolism of various substrates in bacteria and fungi or by Fenton-type reactions, employed in lysosomes. Since iron catalyzed formation of hydroxy radicals can severely damage the host cells as well, iron must be strictly regulated and stored within special compartments in the cells.
Identification of neurodegeneration indicators and disease progression in metachromatic leukodystrophy using quantitative NMR‐based urinary metabolomics
2022-01-27

Abstract Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency of the arylsulfatase A (ARSA). ARSA deficiency leads to an accumulation of sulfatides primarily in the nervous system ultimately causing demyelination. With evolving therapeutic options, there is an increasing need for indicators to evaluate disease progression. Here, we report targeted metabolic urine profiling of 56 MLD patients including longitudinal sampling, using 1 H (proton) nuclear magnetic resonance (NMR) spectroscopy. 1 H‐NMR urine spectra of 119 MLD samples and 323 healthy controls were analyzed by an in vitro diagnostics research (IVDr) tool, covering up to 50 endogenous and 100 disease‐related metabolites on a 600‐MHz IVDr NMR spectrometer. Quantitative data reports were analyzed regarding age of onset, clinical course, and therapeutic intervention. The NMR data reveal metabolome changes consistent with a multiorgan affection in MLD patients in comparison to controls. In the MLD cohort, N‐acetylaspartate (NAA) excretion in urine is elevated. Early onset MLD forms show a different metabolic profile suggesting a metabolic shift toward ketogenesis in comparison to late onset MLD and controls. In samples of juvenile MLD patients who stabilize clinically after hematopoietic stem cell transplantation (HSCT), the macrophage activation marker neopterin is elevated. We were able to identify different metabolic patterns reflecting variable organ disturbances in MLD, including brain and energy metabolism and inflammatory processes. We suggest NAA in urine as a quantitative biomarker for neurodegeneration. Intriguingly, elevated neopterin after HSCT supports the hypothesis that competent donor macrophages are crucial for favorable outcome.
Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets
2022-01-27

Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in vascular smooth muscle cells. Herein we addressed whether acetylation at these sites is also required for the release of CyPA from platelets based on the potential for local delivery of CyPA that may exacerbate cardiovascular disease events. Western blot analyses confirmed the presence of CyPA in human and mouse platelets. Thrombin stimulation resulted in CyPA release from platelets; however, no acetylation was observed—neither in cell lysates nor in supernatants of both untreated and activated platelets, nor after immunoprecipitation of CyPA from platelets. Shotgun proteomics detected two CyPA peptide precursors in the recombinant protein, acetylated at K28, but again, no acetylation was found in CyPA derived from resting or stimulated platelets. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets and that CyPA acetylation is not required for its secretion from platelets.
Dynamic observation of2H labeled compounds in the human brain with1H versus2H magnetic resonance spectroscopy at 9.4T
2022-01-27

Abstract The metabolic pathway of [6,6’- 2 H 2 ]-labeled glucose was investigated with two different techniques. The first technique used direct detection of deuterium applying Deuterium Metabolic Imaging (DMI). The second technique used the indirect detection of deuterium with proton MR spectroscopy (MRS) called Quantitative Exchanged-label Turnover (QELT) MRS. For the first time, time-resolved data was acquired for both techniques in the same healthy human subjects and directly compared. The time-curves were used in a kinetic model to estimate rates of the metabolic pathway of glucose. Two different kinetic models were compared. One included only DMI data, the second one combined DMI and QELT. For the first model, a tricarboxylic acid (TCA) cycle rate of 0.69 ± 0.10 μmol·min -1 ·g -1 was determined. For the second model, the estimated TCA cycle rate was 0.68 ± 0.12 μmol·min -1 ·g -1 . In addition, the rate of glutamine synthesis from glutamate could be estimated with model 2 (0.51 ± 0.15 μmol·min -1 ·g -1 ). The sensitivity of both methods was evaluated and compared to alternative techniques.
A comprehensive evaluation of consensus spectrum generation methods in proteomics
2022-01-27

Abstract Spectrum clustering is a powerful strategy to minimize redundant mass spectral data by grouping highly similar mass spectra corresponding to repeatedly measured analytes. Based on spectrum similarity, near-identical spectra are grouped in clusters, after which each cluster can be represented by its so-called consensus spectrum for downstream processing. Although several algorithms for spectrum clustering have been adequately benchmarked and tested, the influence of the consensus spectrum generation step is rarely evaluated. Here, we present an implementation and benchmark of common consensus spectrum algorithms, including spectrum averaging, spectrum binning, the most similar spectrum, and the best-identified spectrum. We have analyzed diverse public datasets using two different clustering algorithms (spectra-cluster and MaRaCluster) to evaluate how the consensus spectrum generation procedure influences downstream peptide identification. The BEST and BIN methods were found the most reliable methods for consensus spectrum generation, including for datasets with post-translational modifications (PTM) such as phosphorylation. All source code and data of the present study are freely available on GitHub at https://github.com/statisticalbiotechnology/representative-spectra-benchmark .
The Effects of Late Cenozoic Climate Change on the Global Distribution of Frost Cracking
2022-01-27

Abstract. Frost cracking is a dominant mechanical weathering phenomenon facilitating the breakdown of bedrock in periglacial regions. Despite recent advances in understanding frost cracking processes, few studies have addressed how global climate change over the Late Cenozoic may have impacted spatial variations in frost cracking intensity. In this study, we estimate global changes in frost cracking intensity (FCI) by segregation ice growth. Existing process-based models of FCI are applied in combination with soil thickness data from the Harmonized World Soil Database. Temporal and spatial variations in FCI are predicted using surface temperatures changes obtained from ECHAM5 general circulation model simulations conducted for four different paleoclimate time-slices. Time-slices considered include Pre-Industrial (~1850 CE, PI), Mid-Holocene (~6 ka, MH), Last Glacial Maximum (~21 ka, LGM) and Pliocene (~3 Ma, PLIO) times. Results indicate for all paleoclimate time slices that frost cracking was most prevalent (relative to PI times) in the mid to high latitude regions, as well as high-elevation lower latitudes areas such the Himalayas, Tibet, European Alps, the Japanese Alps, the USA Rocky Mountains, and the Andes Mountains. The smallest deviations in frost cracking (relative to PI conditions) were observed in the MH simulation, which yielded slightly higher FCI values in most of the areas. In contrast, larger deviations were observed in the simulations of the colder climate (LGM) and warmer climate (PLIO). Our results indicate that the impact of climate change on frost cracking was most severe during the PI – LGM period due to higher differences in temperatures and glaciation at higher latitudes. In contrast, the PLIO results indicate low FCI in the Andes and higher values of FCI in Greenland and Canada due to the diminished extent of glaciation in the warmer PLIO climate.
Xenobiotic responses in insects
2022-01-28

Abstract Insects have evolved a powerful detoxification system to protect themselves against environmental and anthropogenic xenobiotics including pesticides and nanoparticles. The resulting tolerance to insecticides is an immense problem in agriculture. In this study, we summarize advances in our understanding of insect xenobiotic responses: the detoxification strategies and the regulation mechanisms against xenobiotics including nanoparticles, the problem of response specificity and the potential usefulness of this study field for an elaborate pest management. In particular, we highlight that versatility of the detoxification system relies on the relatively unspecific recognition of a broad range of potential toxic substances that trigger either of various canonical xenobiotic responses signaling pathways, including CncC/Keap1, HR96, AHR/ARNT, GPCR, and MAPK/CREB. However, it has emerged that the actual response to an inducer may nevertheless be specific. There are two nonexclusive possibilities that may explain response specificity: (1) differential cross‐talk between the known pathways and (2) additional, yet unidentified regulators and pathways of detoxification. Hence, a deeper and broader understanding of the regulation mechanisms of xenobiotic response in insects in the future might facilitate the development and application of highly efficient and environmentally friendly pest control methods, allowing us to face the challenge of the world population growth.
Breakup with benefits - hydrothermal mineral systems related to the disintegration of a supercontinent
2022-01-28

Mesozoic hydrothermal systems host the majority of Europe's fluorspar and barite resources as well as significant amounts of metals such as Ag, Co, Zn, Pb, Ni and Cu. Their genetic link to extensional tectonics in conjunction with the opening of the North Atlantic has long been suspected, but their spatial and temporal relation to the tectonic evolution of Europe has remained enigmatic. A thorough evaluation of available geochronological data for fluorite-barite-Pb-Zn, native-metal-arsenide-carbonate and MVT-type mineralization in Continental Europe and North Africa reveals a distinct, as yet unrecognized, time-space relationship between the distribution of hydrothermal mineral systems and the tectonic evolution of the Tethys-Atlantic-Caribbean rift system. The observed time-space relationship and ore-forming mechanisms are evaluated to constrain the underlying driving force for hydrothermal mineralization in the context of the geodynamic evolution of the European lithosphere. Based on this assessment we propose the first continental-scale model for the genesis of Mesozoic hydrothermal ore deposits associated to the breakup of the supercontinent Pangea.
DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber’s hereditary optic neuropathy and optic atrophy
2022-01-28

Background Leber’s hereditary optic neuropathy (LHON) has been considered a prototypical mitochondriopathy and a textbook example for maternal inheritance linked to certain disease-causing variants in the mitochondrial genome. Recently, an autosomal recessive form of LHON (arLHON) has been described, caused by disease-causing variants in the nuclear encoded gene DNAJC30 . Methods and results In this study, we screened the DNAJC30 gene in a large Central European cohort of patients with a clinical diagnosis of LHON or other autosomal inherited optic atrophies (OA). We identified likely pathogenic variants in 35/1202 patients, corresponding to a detection rate of 2.9%. The previously described missense variant c.152A&gt;G;p.(Tyr51Cys) accounts for 90% of disease-associated alleles in our cohort and we confirmed a strong founder effect. Furthermore, we identified two novel pathogenic variants in DNAJC30 : the nonsense variant c.610G&gt;T;p.(Glu204*) and the in-frame deletion c.230_232del;p.(His77del). Clinical investigation of the patients with arLHON revealed a younger age of onset, a more frequent bilateral onset and an increased clinically relevant recovery compared with LHON associated with disease-causing variants in the mitochondrial DNA. Conclusion This study expands previous findings on arLHON and emphasises the importance of DNAJC30 in the genetic diagnostics of LHON and OA in European patients.
On the necessity of essence
2022-01-28

Abstract In the present inquiry, I defend the claim that the thesis that essence is the source of all (metaphysical) necessity is compromised. I argue that, on pain of circularity, essentialists cannot successfully account for the necessity of essences. In response to the difficulties I raise, I discuss potential solutions on behalf of essentialists and explain why I find none of them compelling. My conclusion on the matter is that the best essentialists can hope for is a view where the necessity of essences is left unexplained (by essences).
Pitfalls in the Application of Dispase-Based Keratinocyte Dissociation Assay for In Vitro Analysis of Pemphigus Vulgaris
2022-01-28

Pemphigus vulgaris (PV) is a chronic, life-altering autoimmune disease due to the production of anti-desmoglein antibodies causing the loss of cell–cell adhesion in keratinocytes (acantholysis) and blister formation in both skin and mucous membranes. The dispase-based keratinocyte dissociation assay (DDA) is the method of choice to examine the pathogenic effect of antibodies and additional co-stimuli on cell adhesion in vitro. Despite its widespread use, there is a high variability of experimental conditions, leading to inconsistent results. In this paper, we identify and discuss pitfalls in the application of DDA, including generation of a monolayer with optimized density, appropriate culturing conditions to obtain said monolayer, application of mechanical stress in a standardized manner, and performing consistent data processing. Importantly, we describe a detailed protocol for a successful and reliable DDA and the respective ideal conditions for three different types of human keratinocytes: (1) primary keratinocytes, (2) the HaCaT spontaneously immortalized keratinocyte cell line, and (3) the recently characterized HaSKpw spontaneously immortalized keratinocyte cell line. Our study provides detailed protocols which guarantee intra- and inter-experimental comparability of DDA.
Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
2022-01-28

Background: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) constitute rare chronic inflammatory biliary diseases which likely comprise genetic, environmental and autoimmune factors. Specific inhibitory (auto-) antibodies against the muscarinic acetylcholine receptor type 3 (mAChR3 auto-ab) may contribute to the pathogenesis of chronic biliary inflammation by modulating mAChR3− mediated signaling. Aims: The aim of this study was to analyze the prevalence and relevance of inhibitory mAChR3 auto-ab (mAChR3inh+ auto-ab) in a large cohort of PBC patients from two independent tertiary centers in Berlin and Leipzig in comparison to a large PSC cohort. Baseline parameters and response rates to standard treatment with ursodeoxycholic acid (UDCA) were characterized with respect to the individual mAChR3 auto-ab status. Methods: In total, the study population comprised 437 PBC patients, 187 PSC patients and 80 healthy controls. Clinical and laboratory baseline characteristics were retrieved from medical records. The response to ursodeoxycholic acid (UDCA) therapy after 12 months of treatment was available in 176 PBC and 45 PSC patients. Results: The prevalence of mAChR3inh+ auto-ab was significantly higher among PBC patients (11.2%, 49/437; p = 0.008 vs. healthy controls) and PSC patients (33.6%, 63/187; p &lt; 0.0001 vs. healthy controls) compared to healthy controls (2.5%, 2/80), respectively. PBC patients with mAChR3inh+ auto-ab exhibited significantly higher levels of alkaline phosphatase (ALP) and bilirubin, which constitute established parameters for PBC risk stratification. Moreover, mAChR3inh+ PBC patients tended to show decreased response rates to UDCA therapy compared to PBC patients without mAChR3inh+ auto-ab (mAChR3− PBC). In contrast, PSC patients with mAChR3inh+ auto-ab showed no significant differences in laboratory findings compared to mAChR3 auto-ab negative (mAChR3−) PSC patients. Conclusion: MAChR3inh+ auto-ab might be involved in the pathogenesis and treatment response of chronic biliary inflammation in patients with PBC but not in patients with PSC.
Microbial iron(III) reduction during palsa collapse promotes greenhouse gas emissions before complete permafrost thaw
2022-01-28

&lt;p&gt;Data associated with publication &quot;Microbial iron(III) reduction during palsa collapse promotes greenhouse gas emissions before complete permafrost thaw&quot;. The data contained within this data set is arranged according to the main text and the supplementary information of this publication.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Background information&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;Field site: Stordalen mire, Abisko, Sweden (68 22ʹ N, 19 03ʹ E)&lt;/p&gt; &lt;p&gt;Thaw stages: Palsa, bog and fen&lt;/p&gt; &lt;p&gt;Type of samples: Gas samples, porewater samples, soil core samples&lt;/p&gt;
Microbial iron(III) reduction during palsa collapse promotes greenhouse gas emissions before complete permafrost thaw
2022-01-28

Data associated with publication "Microbial iron(III) reduction during palsa collapse promotes greenhouse gas emissions before complete permafrost thaw". The data contained within this data set is arranged according to the main text and the supplementary information of this publication. <strong>Background information</strong> Field site: Stordalen mire, Abisko, Sweden (68 22ʹ N, 19 03ʹ E) Thaw stages: Palsa, bog and fen Type of samples: Gas samples, porewater samples, soil core samples
Images of Artificial Intelligence: a Blind Spot in AI Ethics
2022-01-29

Abstract This paper argues that the AI ethics has generally neglected the issues related to the science communication of AI. In particular, the article focuses on visual communication about AI and, more specifically, on the use of certain stock images in science communication about AI — in particular, those characterized by an excessive use of blue color and recurrent subjects, such as androgyne faces, half-flesh and half-circuit brains, and variations on Michelangelo’s The Creation of Adam . In the first section, the author refers to a “referentialist” ethics of science communication for an ethical assessment of these images. From this perspective, these images are unethical. While the ethics of science communication generally promotes virtues like modesty and humility, similar images are arrogant and overconfident. In the second section, the author uses French philosopher Jacques Rancière’s concepts of “distribution of the sensible,” “disagreement,” and “pensive image.” Rancière’s thought paves the way to a deeper critique of these images of AI. The problem with similar images is not their lack of reference to the “things themselves.” It rather lies in the way they stifle any possible forms of disagreement about AI. However, the author argues that stock images and other popular images of AI are not a problem per se, and they can also be a resource. This depends on the real possibility for these images to support forms of pensiveness. In the conclusion, the question is asked whether the kind of ethics or politics of AI images proposed in this article can be applied to AI ethics tout court.
Cell‐derived and enzyme‐based decellularized extracellular matrix exhibit compositional and structural differences that are relevant for its use as a biomaterial
2022-01-29

Abstract Due to its availability and minimal invasive harvesting human adipose tissue‐derived extracellular matrix (dECM) is often used as a biomaterial in various tissue engineering and healthcare applications. Next to dECM, cell‐derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. So far both types of ECM were investigated extensively toward their application as (bio)material in tissue engineering and healthcare. However, a systematic characterization and comparison of soft tissue dECM and cdECM is still missing. In this study, we characterized dECM from human adipose tissue, as well as cdECM from human adipose‐derived stem cells, toward their molecular composition, structural characteristics, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans compared with cdECMs. Structural characteristics revealed an immature state of the fibrous part of cdECM samples. By the identified differences, we aim to support researchers in the selection of a suitable ECM‐based biomaterial for their specific application and the interpretation of obtained results.
Accuracy and Interpretability: Struggling with the Epistemic Foundations of Machine Learning-Generated Medical Information and Their Practical Implications for the Doctor-Patient Relationship
2022-01-29

Abstract The initial successes in recent years in harnessing machine learning (ML) technologies to improve medical practice and benefit patients have attracted attention in a wide range of healthcare fields. Particularly, it should be achieved by providing automated decision recommendations to the treating clinician. Some hopes placed in such ML-based systems for healthcare, however, seem to be unwarranted, at least partially because of their inherent lack of transparency, although their results seem convincing in accuracy and reliability. Skepticism arises when the physician as the agent responsible for the implementation of diagnosis, therapy, and care is unable to access the generation of findings and recommendations. There is widespread agreement that, generally, a complete traceability is preferable to opaque recommendations; however, there are differences about addressing ML-based systems whose functioning seems to remain opaque to some degree—even if so-called explicable or interpretable systems gain increasing amounts of interest. This essay approaches the epistemic foundations of ML-generated information specifically and medical knowledge generally to advocate differentiations of decision-making situations in clinical contexts regarding their necessary depth of insight into the process of information generation. Empirically accurate or reliable outcomes are sufficient for some decision situations in healthcare, whereas other clinical decisions require extensive insight into ML-generated outcomes because of their inherently normative implications.