julilili42/papers huggingface dataset:
Reference genome of the antLasius platythorax
2023-07-19

Abstract Ants are a highly diversified insect family of the order Hymenoptera, with many fascinating characteristics such as eusociality, chemical communication, farming, or social parasitism. Moreover, ants frequent a wide variety of habitats from dry deserts, grasslands, and savannas to cold temperate forests. The ability of ants to inhabit such diverse habitat ranges demonstrates their adaptability and ecological resilience. However, little is known about the genetic underpinnings of this vast array of traits and their adaptive potential. Here, we generated a high-quality genome assembly for the ant species Lasius platythorax using long-read PacBio HiFi in combination with chromatin conformation capture (Hi-C) sequencing. We successfully assembled the genome into 15 chromosome-level scaffolds ranging from 7.9 to 19.2 Mb and encompassing 204.6 Mb out of 235.3 Mb (total assembly), and a BUSCO score of 86% (Hymenoptera_odb10). Comparative genomics between the two sister species will provide insights into the genomic basis of trait differentiation.
Novel homozygous LAMB1 in‐frame deletion in a pediatric patient with brain anomalies and cerebrovascular event
2023-07-19

Abstract Biallelic pathogenic variants in LAMB1 have been associated with autosomal recessive lissencephaly 5 (OMIM 615191), which is characterized by brain malformations (cobblestone lissencephaly, hydrocephalus), developmental delay, and epilepsy. Pathogenic variants in LAMB1 are rare, with only 11 pathogenic variants and 11 patients reported to date. Here, we report on a 6‐year‐old patient from a consanguineous family with profound developmental delay, microcephaly, and a history of a perinatal cerebrovascular event. Brain magnetic resonance imaging (MRI) showed cerebellar cystic defects, signal intensity abnormalities, and a hypoplastic corpus callosum. Trio‐exome analysis revealed a homozygous in‐frame deletion of Exons 23 and 24 of LAMB1 affecting 104 amino acids including the epidermal growth factor (EGF)‐like units 11 and 12 in Domain III. To our knowledge, this is the first reported in‐frame deletion in LAMB1 . Our findings broaden the clinical and molecular spectrum of LAMB1 ‐associated syndromes.
Beyond the MEP Pathway: a novel kinase required for prenol utilization by malaria parasites
2023-07-19

Abstract A promising treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, the parasitic source of farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively). Both FPP and GGPP are crucial for the biosynthesis of several essential metabolites such as ubiquinone and dolichol, as well as for protein prenylation. Dietary prenols, such as farnesol (FOH) and geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting the existence of a missing pathway for prenol salvage via phosphorylation, by competition. In this study, we identified a gene in the genome of P. falciparum , encoding a transmembrane prenol kinase (PolK) involved in the salvage of FOH and GGOH. The enzyme was expressed in Saccharomyces cerevisiae , and its FOH/GGOH kinase activities were experimentally validated. Furthermore, conditional gene knockouts were created to investigate the biological importance of the FOH/GGOH salvage pathway. The knockout parasites were viable but more susceptible to fosmidomycin, and their sensitivity to MEP inhibitors could not be rescued by the addition of prenols. Moreover, the knockout parasites lost their ability to use prenols for protein prenylation. These results demonstrate that FOH/GGOH salvage is an additional source of isoprenoids by malaria parasites when de novo biosynthesis is inhibited. This study also identifies a novel kind of enzyme whose inhibition may potentiate the antimalarial efficacy of drugs that affect isoprenoid metabolism.
V28_9 Untargeted Metabolomics Synechococcus elongatus WT vs. delta CutA
2023-07-19

&lt;p&gt;V28_9 Untargeted metabolomics of Synechococcus elongatus sp. PCC 7942 WT or delta CutA in exponential or stationary phase. 5 or 10 uL injections on LC/MS column.&lt;/p&gt;&lt;p&gt;&nbsp;&lt;/p&gt;
Additional file 8 of Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion
2023-07-19

Additional file 8: Suppl. Table S1. Established Melanoma Cell Lines and Patient-Derived Short-Term Cultures with the Respective MAPK Pathway Mutation. Suppl. Table S2. Oligonucleotide Primers for Real-Time Quantitative PCR Analysis. Suppl. Table S3. Primary Antibodies for Western Blot (WB), FACS and Immunohistochemical (IHC) Analyses. Suppl. Table S4. Densitometric Analysis of Immunoblots in Fig. 1A and Suppl. Figure S1A. Suppl. Table S5. Densitometric Analysis of Immunoblots in Fig. 1B and Suppl. Figure S1B. Suppl. Table S6. Densitometric Analysis of Immunoblots in Suppl. Figure S1C. Suppl. Table S7. Densitometric Analysis of Immunoblots in Figure 1C and Suppl. Figure S1E. Suppl. Table S8. Densitometric Analysis of Immunoblots in Suppl. Figure S1D. Suppl. Table S9. Densitometric Analysis of Immunoblots in Fig. 4D. Suppl. Table S10. Densitometric Analysis of Immunoblots in Suppl. Figure S6B. Suppl. Table S11. Densitometric Analysis of Immunoblots in Suppl. Figure S6C. Suppl. Table S12. Densitometric Analysis of Immunoblots in Fig. 5A.
Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk
2023-07-20

Abstract Background and aims Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events. Methods We characterized the platelet lipidome in a large consecutive CAD cohort ( n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. Results The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions. Conclusions Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Graphical abstract Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.
Decoding Mental Effort in a Quasi-Realistic Scenario: A Feasibility Study on Multimodal Data Fusion and Classification
2023-07-20

Humans’ performance varies due to the mental resources that are available to successfully pursue a task. To monitor users’ current cognitive resources in naturalistic scenarios, it is essential to not only measure demands induced by the task itself but also consider situational and environmental influences. We conducted a multimodal study with 18 participants (nine female, M = 25.9 with SD = 3.8 years). In this study, we recorded respiratory, ocular, cardiac, and brain activity using functional near-infrared spectroscopy (fNIRS) while participants performed an adapted version of the warship commander task with concurrent emotional speech distraction. We tested the feasibility of decoding the experienced mental effort with a multimodal machine learning architecture. The architecture comprised feature engineering, model optimisation, and model selection to combine multimodal measurements in a cross-subject classification. Our approach reduces possible overfitting and reliably distinguishes two different levels of mental effort. These findings contribute to the prediction of different states of mental effort and pave the way toward generalised state monitoring across individuals in realistic applications.
A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data
2023-07-20

Abstract MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of &gt;60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms’ role in ecology and human health.
A Combined Western and Bead-Based Multiplex Platform to Characterize Extracellular Vesicles
2023-07-20

In regenerative medicine, extracellular vesicles (EVs) are considered as a promising cell-free approach. EVs are lipid bilayer-enclosed vesicles secreted by cells and are key players in intercellular communication. EV-based therapeutic approaches have unique advantages over the use of cell-based therapies, such as a high biological, but low immunogenic and tumorigenic potential. To analyze the purity and biochemical composition of EV preparations, the International Society for Extracellular Vesicles (ISEV) has prepared guidelines recommending the analysis of multiple (EV) markers, as well as proteins coisolated/recovered with EVs. Traditional methods for EV characterization, such as Western blotting, require a relatively high EV sample/protein input for the analysis of one protein. We here evaluate a combined Western and bead-based multiplex platform, called DigiWest, for its ability to detect simultaneously multiple EV markers in an EV-containing sample with inherent low protein input. DigiWest analysis was performed on EVs from various sources and species, including mesenchymal stromal cells, notochordal cells, and milk, from human, pig, and dog. The study established a panel of nine antibodies that can be used as cross-species for the detection of general EV markers and coisolates in accordance with the ISEV guidelines. This optimized panel facilitates the parallel evaluation of EV-containing samples, allowing for a comprehensive characterization and assessment of their purity. The total protein input for marker analysis with DigiWest was 1 μg for all nine antibodies, compared with ∼10 μg protein input required for traditional Western blotting for one antibody. These findings demonstrate the potential of the DigiWest technique for characterizing various types of EVs in the regenerative medicine field.
CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients—a multicentre study approach, 2021–2022
2023-07-20

Abstract Background In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgarTM provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci. Objectives To assess the applicability of CHROMAgarTM LIN-R in clinical settings for detecting LRE directly from patient material and to infer prevalence rates of LRE amongst German hospital patients. Methods During the 3-month trial period, clinical samples were plated on CHROMAgarTM LIN-R. Antimicrobial susceptibility testing was performed using VITEK2 or disc diffusion. At the NRC, linezolid resistance was determined by broth microdilution, multiplex-PCR for cfr/optrA/poxtA and by a restriction-based assay for 23S rDNA mutations. Results The 12 participating study sites used 13 963 CHROMAgarTM LIN-R plates during the study period. Of 442 presumptive LRE, 192 were confirmed by phenotypic methods. Of these, 161 were received by the NRC and 121 (75%) were verified as LRE. Most of LR-E. faecium 53/81 (65%) exhibited a 23S rRNA gene mutation as the sole resistance-mediating mechanism, whereas optrA constituted the dominant resistance trait in LR-E. faecalis [39/40 (98%)]. Prevalence of LRE across sites was estimated as 1% (ranging 0.18%–3.7% between sites). Conclusions CHROMAgarTM LIN-R represents a simple and efficient LRE screening tool in hospital settings. A high proportion of false-positive results demands validation of linezolid resistance by a reference method.
Occupational resource profiles for an addressee orientation in occupational health management: a segmentation analysis
2023-07-20

Introduction In order to make sustainable decisions in precision prevention and health promotion, it is important to adequately assess people's demands and resources at work. To reach them in an addressee-oriented way, a segmentation of employers and employees based on occupational resources is a promising option. We identified profiles based on personal and perceived organizational resources. Furthermore, we used job demands for profile descriptions to obtain a deeper understanding of the profiles, characterizing people with similar occupational resources. Methods Personal occupational resources (occupational health literacy and self-efficacy) and perceived organizational resources (job decision latitude and participation in health at work) were assessed among employers and employees ( n = 828) in small- and medium-sized enterprises in Germany. Job demands, socioeconomic status, and hierarchy levels in the company were used for further profile descriptions. Results A six-profile solution fitted best to the data based on cluster and profile analyses. One profile was characterized by above-average occupational resources, and another profile was characterized by below-average resources. The other four profiles showed that the individual and perceived organizational resources contrasted. Either organizational resources such as job decision latitude existed and personal resources were not highly developed or people had high individual motivation but few possibilities to participate in health at work. People with medium or high job demands as well as people with low socioeconomic status were most frequently in below-average resource profiles. Employers with high hierarchy levels were overrepresented in the above-average profiles with high organizational resources. Discussion Following the segmentation of the addressees, organizations might be supported in identifying needs and areas for prevention and health promotion. Interventions can be optimally developed, tailored, and coordinated through a deeper understanding of job demands and resources. Especially employees with low socioeconomic status and high job demands might profit from an addressee-orientated approach based on resource profiles. For example, employees obtain an overview of their occupational resource profile to recognize the development potential for safe and healthy behavior at work. Follow-up research should be used to examine how this feedback to employers and employees is implemented and how it affects the sustainability of tailored interventions.
Pars Distalis and Pars Tuberalis Thyroid-Stimulating Hormones and Their Roles in Macro-Thyroid-Stimulating Hormone Formation
2023-07-20

Thyroid-stimulating hormone (TSH) and thyroid hormone levels are standard parameters in blood analysis. However, the immunoassays employed may lead to false-positive or false-negative results when the sample contains certain materials that interfere with the assay. Macro-TSH, a complex of TSH with immunoglobulin or albumin, may cause apparently increased TSH concentrations. TSH is produced in the pars tuberalis (PT) of the pituitary gland and by thyrotrophs of the pars distalis (PD). It was found that variable glycosylation can render the molecule more strongly bound to antibodies or albumin in the blood, leading to the hypothesis that macro-TSH consists mainly of PT-TSH. Although less known than PD-TSH, PT-TSH plays an important role in the central regulation of thyroid metabolism. The present review summarizes the physiological function of human PT-TSH and its role in macro-TSH formation. The prevalence of macro-hyperthyrotropinemia, the structure of PT-TSH and macro-TSH, problems in the measurement of TSH, and the action of PT-TSH in animals with seasonal breeding are discussed. Despite the absence of a specific function of macro-TSH in the organism, the identification of macro-TSH is important for avoiding unnecessary treatment based on a falsified readout of increased TSH concentrations as numerous individual case reports describe.
Training medical students in motivational interviewing using a blended learning approach: a proof-of-concept study
2023-07-20

Background Difficulties in implementing behavior change in patients with chronic diseases are common in clinical practice. Motivational interviewing (MI) helps clinicians to support patients in overcoming ambivalence while maintaining self-determination. The inclusion of MI in German medical training curricula is still rare. Furthermore, the effects of systematic teaching of MI, especially via blended learning, have hardly been investigated. Methods Medical students participated in three curricular events related to MI, consisting of instructional videos and theoretical and practical components in a blended learning format. The aim of the study was to investigate the effect of teaching MI in students’ medical education. A controlled, non-randomized study was conducted with an intervention group and a control group. Both groups completed questionnaires on their experience and knowledge related to MI, completed a knowledge test and rated their satisfaction with the course. MI was taught in the 6th semester of medical coursework as part of a psychosomatic course, in the 8th semester during a psychiatry course and in the 9th semester during a weekly psychiatry clerkship. Results Data from the intervention group ( n = 35) and control group ( n = 14) were analyzed, with 65.7% of students participating in all three parts of the curriculum. Overall interest in learning MI was high, with M = 2.92 ( SD = 1.00). The results indicate a greater increase in knowledge over time in the intervention group. The majority (62.86%) stated that the curriculum was relevant to their future career. Free-form text responses indicated a high level of satisfaction with practical relevance. Conclusion This study demonstrates the usefulness of an MI curriculum for medical students. The integration of MI into medical curricula is a promising curricular addition to improve doctor-patient communication. Future research should address patient perceptions of MI competencies and the persistence of acquired competencies.
N-acetylmuramic acid recognition by MurK kinase from the MurNAc auxotrophic oral pathogen Tannerella forsythia
2023-07-20

The bacterial cell wall consists of a three-dimensional peptidoglycan layer, composed of peptides linked to the sugars N-acetylmuramic acid (MurNAc) and GlcNAc. Unlike other bacteria, the pathogenic Tannerella forsythia, a member of the red complex group of bacteria associated with the late stages of periodontitis, lacks biosynthetic pathways for MurNAc production and therefore obtains MurNAc from the environment. Sugar kinases play a crucial role in the MurNAc recycling process, activating the sugar molecules by phosphorylation. In this study, we present the first crystal structures of a MurNAc kinase, called murein sugar kinase (MurK), in its unbound state as well as in complexes with the ATP analog β-γ-methylene adenosine triphosphate (AMP-PCP) and with MurNAc. We also determined the crystal structures of K1058, a paralogous MurNAc kinase of T. forsythia, in its unbound state and in complex with MurNAc. We identified the active site and residues crucial for MurNAc specificity as the less bulky side chains of S133, P134, and L135, which enlarge the binding cavity for the lactyl ether group, unlike the glutamate or histidine residues present in structural homologs. In establishing the apparent kinetic parameters for both enzymes, we showed a comparable affinity for MurNAc (K<sub>m</sub> 180 μM and 30 μM for MurK and K1058, respectively), with MurK being over two hundred times faster than K1058 (V<sub>max</sub> 80 and 0.34 μmol min<sup>-1</sup> mg<sup>-1</sup>, respectively). These data might support a structure-guided approach to development of inhibitory MurNAc analogs for pathogen MurK enzymes.
Transfer of task-probability-induced biases in parallel dual-task processing occurs in similar, but is constraint in distinct task sets.
2023-07-20

Although humans often multitask, little is known about how the processing of concurrent tasks is managed. The present study investigated whether adjustments in parallel processing during multitasking are local (task-specific) or global (task-unspecific). In three experiments, participants performed one of three tasks: a primary task or, if this task did not require a response, one of two background tasks (i.e., prioritized processing paradigm). To manipulate the degree of parallel processing, we presented blocks consisting mainly of primary or background task trials. In Experiment 1, the frequency manipulation was distributed equally across the two background tasks. In Experiments 2 and 3, only one background task was frequency-biased (inducer task). The other background task was presented equally often in all blocks (diagnostic task) and served to test whether processing adjustments transferred. In all experiments, blocks with frequent background tasks yielded stronger interference between primary and background tasks (primary task performance) and improved background task performance. Thus, resource sharing appeared to increase with high background task probabilities even under triple task requirements. Importantly, these adjustments generalized across the background tasks when they were conceptually and visually similar (Experiment 2). Implementing more distinct background tasks limited the transfer: Adjustments were restricted to the inducer task in background task performance and only small transfer was observed in primary task performance (Experiment 3). Overall, the results indicate that the transfer of adjustments in parallel processing is unrestricted for similar, but limited for distinct tasks, suggesting that task similarity affects the generality of resource allocation in multitasking. (PsycInfo Database Record (c) 2024 APA, all rights reserved).