julilili42/papers huggingface dataset:
Extra-corporeal detoxification in insects
2024-03-21

Upon uptake of toxins, insects launch a detoxification program. This program is deployed in multiple organs and cells to raise their tolerance against the toxin. The molecular mechanisms of this program inside the insect body have been studied and understood in detail. Here, we report on a yet unexplored extra-corporeal detoxification of insecticides in <i>Drosophila melanogaster</i>. Wild-type <i>D. melanogaster</i> incubated with DDT, a contact insecticide, in a closed environment died as expected. However, incubation of a second cohort in the same environment after removal of the dead flies was not lethal. The effect was significantly lower if the flies of the two cohorts were unrelated. Incubation assays with Chlorpyrifos, another contact insecticide, yielded identical results, while incubation assays with Chlorantraniliprole, again a contact insecticide, was toxic for the second cohort of flies. A cohort of flies incubated in a DDT environment after an initial incubation of a honeybee survived treatment. Together, our data suggest that insects including <i>Apis mellifera</i> and <i>D. melanogaster</i> have the capacity to modify their proximate environment. Consequently, in their ecological niche, following individuals might be saved from intoxication thereby facilitating colonisation of an attractive site.
The gases H2and O2in open-culture reactors influence the performance and microbiota of chain elongation inton-caproate andn-caprylate
2024-03-21

Abstract Medium-chain carboxylates are used in various industrial applications. These chemicals are typically extracted from palm oil, which is deemed not sustainable. Recent research has focused on microbial chain elongation using reactors to produce medium-chain carboxylates, such as n -caproate (C6) and n -caprylate (C8), from organic substrates such as wastes. Even though the production of n -caproate is relatively well-characterized, bacteria and metabolic pathways that are responsible for n -caprylate production are not. Here, three 5-L reactors with continuous membrane-based liquid-liquid extraction ( i.e. , pertraction) were fed ethanol and acetate and operated for an operating period of 234 days with different operating conditions. Metagenomic and metaproteomic analyses were employed. n -Caprylate production rates and reactor microbiomes differed between reactors even when operated similarly due to differences in H 2 and O 2 between the reactors. The complete reverse β-oxidation pathway was present and expressed by several bacterial species in the Clostridia class. Several Oscillibacter spp., including Oscillibacter valericigenes , were positively correlated with n -caprylate production rates, while Clostridium kluyveri was positively correlated with n -caproate production. Pseudoclavibacter caeni , which is a strictly aerobic bacterium, was abundant across all the operating periods, regardless of n -caprylate production rates. This study provides insight into microbiota that are associated with n -caprylate production in open-culture reactors and provides ideas for further work. Importance Microbial chain elongation pathways in open-culture biotechnology systems can be utilized to convert organic waste and industrial side streams into valuable industrial chemicals. Here, we investigated the microbiota and metabolic pathways that produce medium-chain carboxylates, including n -caproate (C6) and n -caprylate (C8), in reactors with in-line product extraction. Although the reactors in this study were operated similarly, different microbial communities dominated and were responsible for chain elongation. We found that different microbiota were responsible for n -caproate or n -caprylate production, and this can inform engineers on how to operate the systems better. We also observed which changes in operating conditions steered the production toward and away from n -caprylate, but more work is necessary to ascertain a mechanistic understanding that could be predictive. This study provides pertinent research questions for future work.
Perseverance, a Measure of Conscientiousness, Is a Valid Predictor of Achievement and Truancy Across the Globe
2024-03-21

Is conscientiousness a useful construct across cultures? Using the PISA 2012 data, we examined whether perseverance, a measure of conscientiousness, was related to achievement and truancy across 62 countries/regions (N &amp;gt; 470,000). We investigated whether these relationships were linear or curvilinear in nature and assessed the utility of item-level information. After establishing partial metric invariance of the Perseverance measure across various countries/regions and cultural regions, our findings unveiled that perseverance consistently predicted both math achievement and truancy, with predominantly linear associations. Notably, among the five items of the Perseverance scale, the item reflecting one's tendency to give up easily in the face of challenges emerged as the strongest and most consistent predictor of math achievement. Further, country-level correlations between perseverance and both math achievement and truancy displayed contradictory patterns compared to individual-level correlations, suggesting the presence of biasing factors in how people respond to these measures. Nonetheless, it appears reasonable to conclude that measures of conscientiousness are pan-cultural predictors of achievement and truancy.
Lesions in a songbird vocal circuit increase variability in song syntax
2024-03-21

Abstract Complex motor skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for syntactic ordering of individual actions into sequences is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered sequences of individual syllables. Activity in song premotor nucleus HVC (proper name) has been linked to the control of syllable sequencing, but sequencing may also be affected by its recurrent inputs. We here test the contribution of one of HVC’s inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), to the variable songs of adult male Bengalese finches (Lonchura striata domestica). The syntax of Bengalese song includes several patterns: 1) chunks, where syllables follow stereotypical order 2) branch points, where a given syllable can be followed by two or more different syllables in a probabilistic manner and 3) repeat phrases, where an individual syllable is repeated a variable number of times. We found that after bilateral lesions of mMAN, the acoustic structure of syllables remained largely intact, but sequencing became more variable for each of these patterns, seen by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points and increased variability of repeat numbers. This increase in sequencing variability highlights the potential importance of regions projecting to HVC in the ordering of vocal elements. Previous studies on zebra finches found little effect of mMAN lesions on their relatively stereotyped adult song. In contrast, our results suggest that mMAN contributes to sequencing the variable songs of Bengalese finches and highlight the utility of species with more complex song syntax in investigating neuronal control of ordered motor sequences.
Extreme Outcomes Accentuate Overweighting of Low Probabilities and Underweighting of High Probabilities in Experience‐Based Choice
2024-03-21

ABSTRACT Subjective inferences of probability are critical for decisions involving uncertainty. Recent studies have suggested that extreme outcomes bias beliefs about the value of uncertain options toward the best/worst outcome possible when learning the odds through experience, leading to increased preferences for uncertain options over equivaluable sure bets when there is the prospect of gain and, conversely, aversion to uncertain options when there is the prospect of loss. However, prior studies regarding the influence of extreme outcomes on decisions involving uncertainty have only done so using 50/50 gambles, and it was unclear whether extreme outcomes biased probability perception more broadly. Across three pre‐registered experiments, we found that when people made decisions between equivaluable certain and uncertain options, they particularly preferred uncertain options at low probabilities (20%) when there was the prospect of gain and avoided them when there was the prospect of loss, with these preferences being reduced or even reversed at medium (50%) and high (80%) probabilities. We also found that uncertainty preferences were influenced by outcome extremity and the relative certainty associated with safe reference options. We conclude that extreme outcomes accentuate the overweighting of low probabilities and the underweighting of high probabilities in experience‐based choice.
Author Response: Lesions in a songbird vocal circuit increase variability in song syntax
2024-03-21

Complex motor skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for syntactic ordering of individual actions into sequences is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered sequences of individual syllables. Activity in song premotor nucleus HVC (proper name) has been linked to the control of syllable sequencing, but sequencing may also be affected by its recurrent inputs. We here test the contribution of one of HVC's inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), to the variable songs of adult male Bengalese finches (Lonchura striata domestica). The syntax of Bengalese song includes several patterns: 1) chunks, where syllables follow stereotypical order 2) branch points, where a given syllable can be followed by two or more different syllables in a probabilistic manner and 3) repeat phrases, where an individual syllable is repeated a variable number of times. We found that after bilateral lesions of mMAN, the acoustic structure of syllables remained largely intact, but sequencing became more variable for each of these patterns, seen by 'breaks' in previously stereotyped chunks, increased uncertainty at branch points and increased variability of repeat numbers. This increase in sequencing variability highlights the potential importance of regions projecting to HVC in the ordering of vocal elements. Previous studies on zebra finches found little effect of mMAN lesions on their relatively stereotyped adult song. In contrast, our results suggest that mMAN contributes to sequencing the variable songs of Bengalese finches and highlight the utility of species with more complex song syntax in investigating neuronal control of ordered motor sequences.
Subtle microbial community changes despite rapid glyphosate degradation in microcosms with four German agricultural soils
2024-03-22

Glyphosate is the world's most widely applied herbicide. Despite its extensive and heavy use in agriculture and forestry, the microbial key players involved in glyphosate breakdown and the impact of this compound on the soil microbiota including fungi is not fully understood. Here, we used microcosm experiments to determine the impact of glyphosate application on the microbial community structure and abundance of four different agricultural soils from the Ammer valley, Germany, with a history of glyphosate application. We identified putative glyphosate degraders that could be active under in-situ conditions. Glyphosate was applied to the soils in a single dose of 15 mg·kg−1, which were incubated in the dark with 60 % water-filled pore space at 20 °C for 56 days. Soil samples were taken on the day of glyphosate addition (day 0) and after 7, 28 and 56 days. Capillary electrophoresis-mass spectrometry was used to quantify glyphosate and its major transformation product aminomethylphosphonic acid. Changes in the microbial community structure and abundance were evaluated using 16S rRNA gene or internal transcribed spacer region amplicon sequencing and qPCR. Our findings demonstrate that glyphosate was rapidly degraded in the four soils, with 60–85 % of the applied glyphosate disappearing within 7 days. However, the observed impact of glyphosate application on the microbial community composition was minimal and, notably, there was no significant time-dependent glyphosate effect at 7 days across all four soils. This suggests that glyphosate degradation in soil might be a concerted effort by a wide microbial network or it might be occurring co-metabolically. In addition, the sorption/desorption dynamics of glyphosate with the soil matrix can heavily influence its bioavailability, further reasoning the subtle effects observed on the microbial community structure.
State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms
2024-03-22

Abstract Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.
Atmospheric oxygenation at the onset of Earth’s Great Oxidation forced enhanced marine anoxia
2024-03-22

Abstract Capturing the loss of mass-independent sulphur isotope fractionation (MIF-S), the correlative South African Duitschland and Rooihoogte formations are widely held to bear the isotopic fingerprint of the first atmospheric oxygenation at the onset of the so-called Great Oxidation Event (GOE). Surprisingly, however, while the multiple sulphur isotope systematics of these formations remain central to our understanding of the GOE, until now, comparatively little work has been done to elucidate the repercussions within the marine realm. Here we present chemostratigraphic records from four drill cores covering a large area of the Transvaal Basin, transcending these crucial units and continuing into the overlying Timeball Hill Formation (TBH), that document the immediate, yet counterintuitive, marine response to atmospheric oxygenation. Specifically, irrespective of the interpretative framework employed, our basin-wide redox-sensitive trace element data document an environmental change from oxic/suboxic conditions within the lower and middle parts of the Duitschland and Rooihoogte formations to suboxic/anoxic conditions within their upper reaches. Interestingly, in concert with a ~35‰ negative δ34S excursion that implicates increased sulphate availability and bacterial sulphate reduction, δ98/95Mo3134+0.25 values increase by ~1.0 to 1.5‰. Combining these observations with increased Fe/Mn ratios, elevated total sulphur and carbon contents and a trend towards lower δ13Corg values imply a shift toward less oxygenated conditions across the Transvaal Basin. The combined observations in the mentioned parameters expose a geobiological feedback-driven causality between the earliest oxygenation of the atmosphere and decreased redox potentials of medium to deep marine environments, at least within the Transvaal Basin.
Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals
2024-03-22

<title>Abstract</title> Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large cohort of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND study. Low (0–50 μg/g; n = 602), moderate (&gt; 50–100 μg/g; n = 64) and high (&gt; 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by gut microbiota. Moreover, the high calprotectin group showed increased BMI and more frequent disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.
Evolution of a Meningothelial Meningioma: From WHO Grade 1 to Anaplastic Grade 3 with Extracranial Metastasis Including Extensive Liver Metastasis
2024-03-22

A 61-year-old patient was diagnosed with a left-sided falx meningioma. Histopathological analysis following extirpation showed a meningothelial meningioma ZNS WHO grade 1 with sparse mitoses. Over the course of 12 years, the patient received irradiation (54.0 Gy), peptide radio-receptor therapy (177Lu-DOMITATE) and targeted therapy (mTOR inhibitor). Follow-up imaging revealed an increased size of the residual tumor. Due to increased liver function parameters, imaging of the liver was performed, showing widespread space-occupying lesions with atypical appearance. Biopsy revealed metastasis of the meningioma, now with 2.7 mitoses/mm2, necrosis and homozygous CDKN2A/B deletion, corresponding to an anaplastic CNS meningioma WHO grade 3. A second small meningioma on the left petroclival side has been consistent in size over 12 years. Metastatic meningiomas pose a pertinent clinical challenge due to poor prognosis. The lung, bone, liver and cervical lymph nodes are the most common sites of extracranial metastasis. According to the World Health Organization criteria, the most important predictive factor for recurrence and metastasis is the tumor grade.
Abstract 3986: Exploring nonsense-mediated decay inhibition as a novel approach to improve immunogenicity in small cell lung cancer
2024-03-22

Abstract Cancer immunotherapy has revolutionized the field of oncology and is one of the most promising treatments for lung cancer. Small cell lung cancer (SCLC) is highly aggressive and patients often relapse due to chemotherapy resistance. In the recent years, chemotherapy has been combined with immune checkpoint inhibition (ICI) for SCLC treatment, leading to improved responses in some patients, but also leaving a high number of non-responders to address. Paradoxically, SCLC has one of the highest tumor mutational burden, including remarkably abundant frameshifts (FS) which could create highly immunogenic neoantigens (NeoAg). However, FS-harbouring transcripts are often degraded via Nonsense-Mediated Decay (NMD). We therefore aimed to inhibit the NMD pathway to increase the immunogenicity of SCLC. Our lab has so far profiled the mutational landscape of more than 400 SCLC patients and generated over 100 patient-derived xenotransplant models. We analyzed genome and transcriptome sequencing data of multiple tumors to interrogate the NMD target repertoire in SCLC. We determined tumor-specific mutations and predicted NeoAg based on the HLA-I-binding ability of mutant peptides. Upon NMD inhibiton, we validated the expression and presentation of NeoAg via transcriptomics, proteomics and HLA-I-immunopeptidomics. NMD-sensitive mutated transcripts included a wide range of somatic alterations beyond FS-mutations, suggesting an overall increase of potential tumor-specific NeoAg. We furthermore evaluated immunogenicity after NMD perturbation employing in vitro co-cultures as well as immunocompetent in vivo mouse models. Inhibition of NMD in tumor cells resulted in an HLA-I-dependent enhancement of T cell-mediated tumor killing in vitro, and in vivo experiments showed reduced tumor growth accompanied by increased immune infiltration upon controlled induction of NMD inhibition. Altogether, NMD inhibition in SCLC led to an upregulation of NeoAg expression in tumor cells accompanied by enhanced T cell responses in vitro and in vivo. Our strategy provides a novel approach for the treatment of low immunogenic tumors which could be combined with ICI to enhance the efficacy of immunotherapy. Citation Format: Lucia A. Torres Fernández, Volker Böhm, Lukas Maas, Anna Schöllhorn, Joel Kaufmann, Joshua D'Rozario, Laura Kaiser, Niels Gehring, Martin Peifer, Cécile Gouttefangeas, Roman K. Thomas, Julie George. Exploring nonsense-mediated decay inhibition as a novel approach to improve immunogenicity in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3986.
Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs
2024-03-22

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.