julilili42/papers huggingface dataset:
Mapping temperature-sensitive mutations at a genome-scale to engineer growth-switches inE. coli
2023-06-02

Abstract Temperature-sensitive (TS) mutants are a unique tool to perturb and engineer cellular systems. Here, we constructed a CRISPR library with 15,120 Escherichia coli mutants, each with a single amino acid change in one of 346 essential proteins. 1,269 of these mutants showed temperature-sensitive growth in a time-resolved competition assay. We reconstructed 94 TS mutants and measured their metabolism under growth arrest at 42°C using metabolomics. Metabolome changes were strong and mutant-specific, showing that metabolism of non-growing E. coli is perturbation-dependent. For example, 24 TS mutants of metabolic enzymes overproduced the direct substrate-metabolite due to a bottleneck in their associated pathway. A strain with TS homoserine kinase (ThrB F267D ) produced homoserine for 24 hours, and production was tunable by temperature. Finally, we used a TS subunit of DNA polymerase III (DnaX L289Q ) to decouple growth from arginine overproduction in engineered E. coli . These results provide a strategy to identify TS mutants en masse and demonstrate their large potential to produce bacterial metabolites with non-growing cells.
Unnatural endo type-B PPAPs as novel compounds with activity against Mycobacterium tuberculosis.
2023-06-02

Before the emergence of SARS-CoV-2, tuberculosis (TB) was the leading cause of infectious disease mortality worldwide. Like all antibiotic-exposed bacteria Mycobacterium tuberculosis (Mtb) developed multidrug-resistant (MDR) and exten-sively drug-resistant (XDR) strains which require new antibiotics with novel mechanism of actions. Hyperforin, a natural type-A polyprenylated polycyclic acylphloroglucinol (PPAP) isolated from St. John’s wort, is known for its antibacterial, antidepressant and antimycobacterial activity. However, hyperforin is not stable and easily degradable in light, heat it and oxidizes. Here we report photo- and benchstable type-B PPAPs with structural similarity to hyperforin and enhanced an-timycobacterial activity. We tested a panel of PPAPs and identified our previously reported molecule PPAP22 as lead compound. Converting PPAP22 into the corresponding sodium salt, PPAP53, enhanced the solubility dramatically. We show that PPAP53 inhibits the growth of virulent, extracellular Mtb. Strikingly, the activity is more pronounced intracel-lular Mtb residing in human primary macrophages without damaging the host cell or lung cells. Importantly PPAP53 was also highly active against drug-resistant Mtb. Additionally, we analysed the in vitro properties of PPAP53 in terms of CYP-induction and PXR interaction. Taken together we introduce type-B PPAPs are a new class of antimycobacterial com-pounds, with remarkable activity and favorouble physical properties.
Time series of electrical conductivity, temperature, relative stream stage and total pressure recorded in surface water and streambed sediments of River Erpe and River Ammer, Germany, and the Sturt River, South Australia
2023-06-02

&lt;p&gt;Time series of electrical conductivity (mS cm&lt;sup&gt;-1&lt;/sup&gt;), temperature (degC), relative stream stage (cm) and total pressure (hPa) recorded in the surface water and in streambed sediments (depth in cm) of River Erpe and River Ammer, Germany, and the Sturt River, South Australia.&lt;/p&gt;
Time series of electrical conductivity, temperature, relative stream stage and total pressure recorded in surface water and streambed sediments of River Erpe and River Ammer, Germany, and the Sturt River, South Australia
2023-06-02

Time series of electrical conductivity (mS cm<sup>-1</sup>), temperature (degC), relative stream stage (cm) and total pressure (hPa) recorded in the surface water and in streambed sediments (depth in cm) of River Erpe and River Ammer, Germany, and the Sturt River, South Australia.
A patent review of MAPK inhibitors (2018 – present)
2023-06-03

Although industrial research on MAPK-inhibitors has been ongoing for more than 20 years, novel clinical trials of MAPK-inhibitors as potential drug candidates are still being conducted in the period under review. Recently reported inhibitors show an excellent selectivity profile and are even achieving selectivity between closely related isoforms. This progression offers the possibility to eliminate unwanted side effects and may finally lead to the approval of the first MAPK-inhibitor.
Autotrophic growth of E. coli is achieved by a small number of genetic changes
2023-06-03

Abstract Synthetic autotrophy is a promising avenue to sustainable bioproduction from CO 2 . Here, we use iterative laboratory evolution to generate several distinct autotrophic strains. Utilising this genetic diversity, we identify that just three mutations are sufficient for E. coli to grow autotrophically, when introduced alongside non-native energy (formate dehydrogenase) and carbon-fixing (RuBisCO, phosphoribulokinase, carbonic anhydrase) modules. The mutated genes are involved in glycolysis ( pgi ), central-carbon regulation ( crp ), and RNA transcription ( rpoB ). The pgi mutation reduces the enzyme’s activity, thereby stabilising the carbon-fixing cycle by capping a major branching flux. For the other two mutations, we observe down-regulation of several metabolic pathways and increased expression of native genes associated with the carbon-fixing module ( rpiB ) and the energy module ( fdoGH ), as well as an increased ratio of NADH/NAD+ - the cycle’s electron-donor. This study demonstrates the malleability of metabolism and its capacity to switch trophic modes using only a small number of genetic changes and could facilitate transforming other heterotrophic organisms into autotrophs.
Plant community productivity and soil water are not resistant to extreme experimental drought in temperate grasslands but in the understory of temperate forests
2023-06-04

Climate change is continuously intensifying droughts. Extreme droughts are expected to reduce soil water content and thus, ecosystem functioning such as above-ground primary productivity. Nonetheless, results of experimental drought studies vary from no impact to a significant decrease in soil water content and/or productivity. We experimentally imposed extreme drought as 30 % and 50 % precipitation reductions using rainout shelters for four years in temperate grasslands and in the forest understory. We studied the concurrent impact of two intensities of extreme drought on the soil water content and above-ground primary productivity in the last experimental year (resistance). Furthermore, we observed resilience as the extent to which both variables differ from ambient conditions after the removal of the 50 % reduction. We show a systematic difference in response to extreme experimental drought between grasslands and the forest understory irrespective of the intensity of the extreme drought. Namely, extreme drought resulted in a significant decrease of the soil water content and productivity in grasslands but not in the forest understory. Interestingly, the negative impacts in the grasslands did not persist as evidenced by the fact that soil water content and productivity were similar to ambient conditions after the removal of the drought. Our results indicate that extreme drought on small spatial scales does not necessarily result in a concurrent soil water decrease in the forest understory, while this is the case for grasslands, with respective consequences for the resistance of productivity. Grasslands, however, can be resilient. Our study highlights that considering the response of the soil water content is key to understanding divergent productivity responses to extreme drought among different ecosystems.
Parental Leave Policies, Usage Consequences, and Changing Normative Beliefs: Evidence From a Survey Experiment
2023-06-04

In this study, we conceptualize and provide novel empirical evidence on norm-setting effects of family policies by investigating how priming with parental leave policy–related information may alter normative beliefs regarding the gender division of parental leave in Germany. We implemented a survey experiment in two waves of the representative German GESIS Panel in 2019 and 2020. Respondents received one of three short evidence-based information primers about (1) long-term income risks of maternal employment interruptions, (2) nonsignificant paternal wage penalties, or (3) increasing rates of paternal leave usage in Germany, or were allocated to the control group that received no further information before rating the division of parental leave in fictitious couples. We apply ordinary least squares regression models with lagged dependent variables to a sample of 5,362 vignette evaluations nested in 1,548 respondents. Remarkably, we find that the effects of all three priming conditions vary significantly depending on whether respondents are asked to judge situations for couples where women earn more or less than their partners. Our findings mostly point to stronger effects of priming with information on income risks compared with paternal leave usage trends and to more pronounced changes in normative beliefs among childless respondents.
Attack Simulation and Adaptation in CAN for Training and Evaluation of IDS
2023-06-04

The vulnerability of vehicles due to the lack of security features of the Controller Area Network (CAN) is now well known. CAN is one of the de facto standards for internal vehicle communication, so securing CAN against attacks is an ongoing challenge. For this purpose, Intrusion Detection Systems (IDS) are a widely known approach for attack detection. IDS have to be trained and evaluated, therefore data is needed. The few publicly available data sets cover only a small variance of possible attacks. Since conducting real attacks can be a costly business, the presented method generates simulated attack data that can be used to train and evaluate IDS. To show the vulnerabilities of an IDS, the approach adapted the attacks so that they are not detected by the IDS. The approach is executed on an IDS that detected 99.99% of the original attacks in the publicly available data sets. After adaptation by the proposed method, we found several attacks that were not detected.
Biotite: new tools for a versatile Python bioinformatics library
2023-06-05

Abstract Background Biotite is a program library for sequence and structural bioinformatics written for the Python programming language. It implements widely used computational methods into a consistent and accessible package. This allows for easy combination of various data analysis, modeling and simulation methods. Results This article presents major functionalities introduced into Biotite since its original publication. The fields of application are shown using concrete examples. We show that the computational performance of Biotite for bioinformatics tasks is comparable to individual, special purpose software systems specifically developed for the respective single task. Conclusions The results show that Biotite can be used as program library to either answer specific bioinformatics questions and simultaneously allow the user to write entire, self-contained software applications with sufficient performance for general application.
Do you have a good all-around view? Evaluation of a decision-making skills diagnostic tool using 360° videos and head-mounted displays in elite youth soccer
2023-06-05

Elite youth players’ decision-making skills are considered important predictors of adult performance in soccer. The presentation of 360° videos in head-mounted displays offers new potential for the diagnostic of these skills in talent development programs. This study evaluated a new diagnostic tool using soccer-specific 360° videos for assessing decision-making skills in youth academy (YA) players. The evaluation consisted of players' subjective feedback as well as the analysis of diagnostic and prognostic validity. It was hypothesized that high-level YA players achieve better diagnostic results than regional-level players, and U19 outperform U17 players. Moreover, YA players' diagnostic results should be positively associated with future adult performance level. During the 2018/19 season, N = 48 youth players participated in the diagnostic procedures (split-half reliability r = .78). Participants were shown 54 videos which terminated when the central midfielder received a teammate's pass. Participants were then asked how to best continue playing. The subjective evaluation explored YA players' experiences with the diagnostic tool via quantitative ratings (e.g., “How exciting was the task?”, “How involved did you feel in the game situation?”) and additional interviews. Diagnostic validity was examined in a balanced cross-sectional 2 × 2-design (performance level x age group) and prognostic validity in a 3-year prospective design. Sensitivity and case-by-case analyses completed the evaluation. The YA players provided positive quantitative ratings regarding their experienced immersion into the environment. Players’ qualitative feedback indicated general acceptance of the diagnostic tool as well as it offered recommendations for improvements. Confirming the diagnostic validity, ANOVA revealed significant main effects for performance level ( p &amp;lt; .001, η 2 = .29) and age group ( p &amp;lt; .01, η 2 = .14). Contributing to the prognostic validity, the diagnostic results discriminated between YA players achieving a higher and a lower adult performance level (“League 1–4” vs. “League 5 or below”) in adulthood ( p &amp;lt; .05; d = 0.80). A ROC curve and the AUC showed that the correct assignment to the adult performance levels is possible with a 71% probability. YA players with a high decision-making accuracy had a six times higher chance of playing in “League 1–4”. The results demonstrated empirical evidence for the new diagnostic tool in terms of YA players' acceptance and validity coefficients exceeding effect sizes of former studies. The technology provides opportunities to test soccer-specific situations demanding an all-around view that were not testable in former experimental settings. Further technological advancements will enable the realization of improvements recommended by the players. Nonetheless, case-by-case analyses suggest caution in using such a diagnostic as a selection tool in talent development programs.
Psychological restoration depends on curiosity, motivation, and species richness during a guided bird walk in a suburban blue space
2023-06-05

Urban and suburban green and blue spaces are important places for human recreation, and the impact of biodiversity on psychological and recalled restoration has received much attention. This study addresses the relationship between bird species richness and restoration in a controlled field experiment (guided bird walk) applying a battery of individual trait scales (need for cognition, personality) as predictors of restoration. We found a significant positive relationship between the number of bird species present and recalled restoration. Personality, bird species knowledge, bird related interest as test measures, demographics and birding specialization as self-report had no influence on psychological restoration. However, need for cognition correlated positively with psychological restoration, thus providing a new predictive variable. All subscales of the intrinsic motivation scale (enjoyment, perceived competence, perceived choice, pressure/tension) were positively correlated with restoration except of pressure/tension. Learning emotions like interest and well-being were positively related to restoration, while boredom was negatively related. Therefore, we suggest research to examine the restorative function of more cognitive-oriented programs because people may also need cognition when it comes to restoration. We also suggest a broader focus on education and cognitive aspects when it comes to linking biodiversity and health within the framework of ecosystem services.
NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
2023-06-05

Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer’s disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus–receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus–receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that central NgR1 surfaces form a bridge between two copies of viral capsid protein σ3, establishing that σ3 serves as a receptor ligand for reovirus. This unusual binding interface produces high-avidity interactions between virus and receptor to prime early entry steps. These studies refine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.
Association of extent of resection on recurrence-free survival and functional outcome in vestibular schwannoma of the elderly
2023-06-05

Background Despite the ongoing debate on the risk–benefit ratio of vestibular schwannoma (VS) treatment options, watchful observation and radiation are usually favored in the elderly (&amp;gt;65 years). If surgery is inevitable, a multimodal approach after deliberate subtotal resection has been described as a valid option. The relationship between the extent of resection (EOR) of surgical and functional outcomes and recurrence-free survival (RFS) remains unclear. This present study aims to evaluate the functional outcome and RFS of the elderly in relation to the EOR. Methods This matched cohort study analyzed all consecutive elderly VS patients treated at a tertiary referral center since 2005. A separate cohort (&amp;lt;65 years) served as a matched control group (young). Clinical status was assessed by the Charlson Comorbidity Index (CCI), the Karnofsky Performance (KPS), and the Gardner and Robertson (GR) and House &amp;amp; Brackmann (H&amp;amp;B) scales. RFS was evaluated by Kaplan–Meier analysis using contrast-enhanced magnetic resonance imaging to identify tumor recurrence. Results Among 2,191 patients, 296 (14%) patients were classified as elderly, of whom 133 (41%) were treated surgically. The elderly were characterized by a higher preoperative morbidity and worse gait uncertainty. Postoperative mortality (0.8% and 1%), morbidity (13% and 14%), and the functional outcome (G&amp;amp;R, H&amp;amp;B, and KPS) did not differ between the elderly and the young. There was a significant benefit in regard to the preoperative imbalance. Gross total resection (GTR) was accomplished in 74% of all cases. Lower grades of the EOR (subtotal and decompressive surgery) raised the incidence of recurrence significantly. Mean time to recurrence in the surg ELDERLY was 67.33 ± 42.02 months and 63.2 ± 70.98 months in the surgCONTROL . Conclusions Surgical VS treatment aiming for complete tumor resection is feasible and safe, even in advanced age. A higher EOR is not associated with cranial nerve deterioration in the elderly compared to the young. In contrast, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. If surgery is indicated in the elderly, GTR can be intended safely, and if only subtotal resection is achieved, further adjuvant therapy, e.g., radiotherapy, should be discussed in the elderly, as the incidence of recurrence is not significantly lower compared to the young.
Whole-Body Magnetic Resonance Imaging (MRI) for Staging Melanoma Patients in Direct Comparison to Computed Tomography (CT): Results from a Prospective Positron Emission Tomography (PET)/CT and PET/MRI Study
2023-06-05

Purpose: The consideration of radiation exposure is becoming more important in metastatic melanoma due to improved prognoses. The aim of this prospective study was to investigate the diagnostic performance of whole-body (WB) magnetic resonance imaging (MRI) in comparison to computed tomography (CT) with 18F-FDG positron emission tomography (PET)/CT and 18F-PET/MRI together with a follow-up as the reference standard. Methods: Between April 2014 and April 2018, a total of 57 patients (25 females, mean age of 64 ± 12 years) underwent WB-PET/CT and WB-PET/MRI on the same day. The CT and MRI scans were independently evaluated by two radiologists who were blinded to the patients’ information. The reference standard was evaluated by two nuclear medicine specialists. The findings were categorized into different regions: lymph nodes/soft tissue (I), lungs (II), abdomen/pelvis (III), and bone (IV). A comparative analysis was conducted for all the documented findings. Inter-reader reliability was assessed using Bland–Altman procedures, and McNemar’s test was utilized to determine the differences between the readers and the methods. Results: Out of the 57 patients, 50 were diagnosed with metastases in two or more regions, with the majority being found in region I. The accuracies of CT and MRI did not show significant differences, except in region II where CT detected more metastases compared to MRI (0.90 vs. 0.68, p = 0.008). On the other hand, MRI had a higher detection rate in region IV compared to CT (0.89 vs. 0.61, p &gt; 0.05). The level of agreement between the readers varied depending on the number of metastases and the specific region, with the highest agreement observed in region III and the lowest observed in region I. Conclusions: In patients with advanced melanoma, WB-MRI has the potential to serve as an alternative to CT with comparable diagnostic accuracy and confidence across most regions. The observed limited sensitivity for the detection of pulmonary lesions might be improved through dedicated lung imaging sequences.