Refine
Year of publication
- 2022 (330) (remove)
Document Type
- Preprint (330) (remove)
Language
- English (330)
Has Fulltext
- yes (330)
Is part of the Bibliography
- no (330)
Keywords
Institute
- Physik (190)
- Frankfurt Institute for Advanced Studies (FIAS) (144)
- Informatik (102)
- Medizin (28)
- Ernst Strüngmann Institut (25)
- Biowissenschaften (22)
- Senckenbergische Naturforschende Gesellschaft (8)
- MPI für Hirnforschung (7)
- Psychologie (6)
- Biochemie, Chemie und Pharmazie (5)
We investigate the impact of non-Hermiticity on the thermodynamic properties of interacting fermions by examining bilinear extensions to the 3+1 dimensional SU(2)-symmetric Nambu--Jona-Lasinio (NJL) model of quantum chromodynamics at finite temperature and chemical potential. The system is modified through the anti-PT-symmetric pseudoscalar bilinear ψ¯γ5ψ and the PT-symmetric pseudovector bilinear iBνψ¯γ5γνψ, introduced with a coupling g. Beyond the possibility of dynamical fermion mass generation at finite temperature and chemical potential, our findings establish model-dependent changes in the position of the chiral phase transition and the critical end-point. These are tunable with respect to g in the former case, and both g and |B|/B0 in the latter case, for both lightlike and spacelike fields. Moreover, the behavior of the quark number, entropy, pressure and energy densities signal a potential fermion or antifermion excess compared to the standard NJL model, due to the pseudoscalar and pseudovector extension respectively. In both cases regions with negative interaction measure I=ϵ−3p are found. Future indications of such behaviors in strongly interacting fermion systems, for example in the context of neutron star physics, may point toward the presence of non-Hermitian contributions. These trends provide a first indication of curious potential mechanisms for producing non-Hermitian baryon asymmetry. In addition, the formalism described in this study is expected to apply more generally to other Hamiltonians with four-fermion interactions and thus the effects of the non-Hermitian bilinears are likely to be generic.
We investigate the impact of non-Hermiticity on the thermodynamic properties of interacting fermions by examining bilinear extensions to the 3+1 dimensional SU(2)-symmetric Nambu--Jona-Lasinio (NJL) model of quantum chromodynamics at finite temperature and chemical potential. The system is modified through the anti-PT-symmetric pseudoscalar bilinear ψ¯γ5ψ and the PT-symmetric pseudovector bilinear iBνψ¯γ5γνψ, introduced with a coupling g. Beyond the possibility of dynamical fermion mass generation at finite temperature and chemical potential, our findings establish model-dependent changes in the position of the chiral phase transition and the critical end-point. These are tunable with respect to g in the former case, and both g and |B|/B0 in the latter case, for both lightlike and spacelike fields. Moreover, the behavior of the quark number, entropy, pressure, and energy densities signal a potential fermion or antifermion excess compared to the standard NJL model, due to the pseudoscalar and pseudovector extension respectively. In both cases regions with negative interaction measure I=ϵ−3p are found. Future indications of such behaviors in strongly interacting fermion systems, for example in the context of neutron star physics, may point toward the presence of non-Hermitian contributions. These trends provide a first indication of curious potential mechanisms for producing non-Hermitian baryon asymmetry. In addition, the formalism described in this study is expected to apply more generally to other Hamiltonians with four-fermion interactions and thus the effects of the non-Hermitian bilinears are likely to be generic.
Chern numbers can be calculated within a frame of vortex fields related to phase conventions of a wave function. In a band protected by gaps the Chern number is equivalent to the total number of flux carrying vortices. In the presence of topological defects like Dirac cones this method becomes problematic, in particular if they lack a well-defined winding number. We develop a scheme to include topological defects into the vortex field frame. A winding number is determined by the behavior of the phase in reciprocal space when encircling the defect's contact point. To address the possible lack of a winding number we utilize a more general concept of winding vectors. We demonstrate the usefulness of this ansatz on Dirac cones generated from bands of the Hofstadter model.
Chern numbers can be calculated within a frame of vortex fields related to phase conventions of a wave function. In a band protected by gaps the Chern number is equivalent to the total number of flux carrying vortices. In the presence of topological defects like Dirac cones this method becomes problematic, in particular if they lack a well-defined winding number. We develop a scheme to include topological defects into the vortex field frame. A winding number is determined by the behavior of the phase in reciprocal space when encircling the defect's contact point. To address the possible lack of a winding number we utilize a more general concept of winding vectors. We demonstrate the usefulness of this ansatz on Dirac cones generated from bands of the Hofstadter model.
Abstract
Natural plant populations often harbour substantial heritable variation in DNA methylation. However, a thorough understanding of the genetic and environmental drivers of this epigenetic variation requires large-scale and high-resolution data, which currently exist only for a few model species. Here, we studied 207 lines of the annual weed Thlaspi arvense (field pennycress), collected across a large latitudinal gradient in Europe and propagated in a common environment. By screening for variation in DNA sequence and DNA methylation using whole-genome (bisulfite) sequencing, we found significant epigenetic population structure across Europe. Average levels of DNA methylation were strongly context-dependent, with highest DNA methylation in CG context, particularly in transposable elements and in intergenic regions. Residual DNA methylation variation within all contexts was associated with genetic variants, which often co-localized with annotated methylation machinery genes but also with new candidates. Variation in DNA methylation was also significantly associated with climate of origin, with methylation levels being higher in warmer regions and lower in more variable climates. Finally, we used variance decomposition to assess genetic versus environmental associations with differentially methylation regions (DMRs). We found that while genetic variation was generally the strongest predictor of DMRs, the strength of environmental associations increased from CG to CHG and CHH, with climate-of-origin as the strongest predictor in about one third of the CHH DMRs. In summary, our data show that natural epigenetic variation in Thlaspi arvense is significantly associated with both DNA sequence and environment of origin, and that the relative importance of the two factors strongly depends on the sequence context of DNA methylation. T. arvense is an emerging biofuel and winter cover crop; our results may hence be relevant for breeding efforts and agricultural practices in the context of rapidly changing environmental conditions.
Author Summary: Variation within species is an important level of biodiversity, and it is key for future adaptation. Besides variation in DNA sequence, plants also harbour heritable variation in DNA methylation, and we want to understand the evolutionary significance of this epigenetic variation, in particular how much of it is under genetic control, and how much is associated with the environment. We addressed these questions in a high-resolution molecular analysis of 207 lines of the common plant field pennycress (Thlaspi arvense), which we collected across Europe, propagated under standardized conditions, and sequenced for their genetic and epigenetic variation. We found large geographic variation in DNA methylation, associated with both DNA sequence and climate of origin. Genetic variation was generally the stronger predictor of DNA methylation variation, but the strength of environmental association varied between different sequence contexts. Climate-of-origin was the strongest predictor in about one third of the differentially methylated regions in the CHH context, which suggests that epigenetic variation may play a role in the short-term climate adaptation of pennycress. As pennycress is currently being domesticated as a new biofuel and winter cover crop, our results may be relevant also for agriculture, particularly in changing environments.
The mammalian frontal and auditory cortices are important for vocal behaviour. Here, using local field potential recordings, we demonstrate for the first time that the timing and spatial pattern of oscillations in the fronto-auditory cortical network of vocalizing bats (Carollia perspicillata) predict the purpose of vocalization: echolocation or communication. Transfer entropy analyses revealed predominantly top-down (frontal-to-auditory cortex) information flow during spontaneous activity and pre-vocal periods. The dynamics of information flow depended on the behavioural role of the vocalization and on the timing relative to vocal onset. Remarkably, we observed the emergence of predominantly bottom-up (auditory-to-frontal cortex) information transfer patterns specific echolocation production, leading to self-directed acoustic feedback. Electrical stimulation of frontal areas selectively enhanced responses to echolocation sounds in auditory cortex. These results reveal unique changes in information flow across sensory and frontal cortices, potentially driven by the purpose of the vocalization in a highly vocal mammalian model.
More than 75% of surface and secreted proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, influencing protein dynamics and interactions with other molecules. Glycan conformational freedom impairs complete structural elucidation of glycoproteins. Computer simulations may be used to model glycan structure and dynamics. However, such simulations typically require thousands of computing hours on specialized supercomputers, thus limiting routine use. Here, we describe a reductionist method that can be implemented on personal computers to graft ensembles of realistic glycan conformers onto static protein structures in a matter of minutes. Using this open-source pipeline, we reconstructed the full glycan cover of SARS-CoV-2 Spike protein (S-protein) and a human GABAA receptor. Focusing on S-protein, we show that GlycoSHIELD recapitulates key features of extended simulations of the glycosylated protein, including epitope masking, and provides new mechanistic insights on N-glycan impact on protein structural dynamics.
The human brain achieves visual object recognition through multiple stages of nonlinear transformations operating at a millisecond scale. To predict and explain these rapid transformations, computational neuroscientists employ machine learning modeling techniques. However, state-of-the-art models require massive amounts of data to properly train, and to the present day there is a lack of vast brain datasets which extensively sample the temporal dynamics of visual object recognition. Here we collected a large and rich dataset of high temporal resolution EEG responses to images of objects on a natural background. This dataset includes 10 participants, each with 82,160 trials spanning 16,740 image conditions. Through computational modeling we established the quality of this dataset in five ways. First, we trained linearizing encoding models that successfully synthesized the EEG responses to arbitrary images. Second, we correctly identified the recorded EEG data image conditions in a zero-shot fashion, using EEG synthesized responses to hundreds of thousands of candidate image conditions. Third, we show that both the high number of conditions as well as the trial repetitions of the EEG dataset contribute to the trained models’ prediction accuracy. Fourth, we built encoding models whose predictions well generalize to novel participants. Fifth, we demonstrate full end-to-end training of randomly initialized DNNs that output M/EEG responses for arbitrary input images. We release this dataset as a tool to foster research in visual neuroscience and computer vision.
NAD is a coenzyme central to metabolism that was also found to serve as a 5’-terminal cap of bacterial and eukaryotic RNA species. The presence and functionality of NAD-capped RNAs (NAD-RNAs) in the archaeal domain remain to be characterized in detail. Here, by combining LC-MS and NAD captureSeq methodology, we quantified the total levels of NAD-RNAs and determined the identity of NAD-RNAs in the two model archaea, Sulfolobus acidocaldarius and Haloferax volcanii. A complementary differential RNA-Seq (dRNA-Seq) analysis revealed that NAD transcription start sites (NAD-TSS) correlate with well-defined promoter regions and often overlap with primary transcription start sites (pTSS). The population of NAD-RNAs in the two archaeal organisms shows clear differences, with S. acidocaldarius possessing more capped small non-coding RNAs (sncRNAs) and leader sequences. The NAD-cap did not prevent 5’→3’ exonucleolytic activity by the RNase Saci-aCPSF2. To investigate enzymes that facilitate the removal of the NAD-cap, four Nudix proteins of S. acidocaldarius were screened. None of the recombinant proteins showed NAD decapping activity. Instead, the Nudix protein Saci_NudT5 showed activity after incubating NAD-RNAs at elevated temperatures. Hyperthermophilic environments promote the thermal degradation of NAD into the toxic product ADPR. Incorporating NAD into RNAs and the regulation of ADPR-RNA decapping by Saci_NudT5 is proposed to provide additional layers of maintaining stable NAD levels in archaeal cells.
Importance: This study reports the first characterization of 5’-terminally modified RNA molecules in Archaea and establishes that NAD-RNA modifications, previously only identified in the other two domains of life, are also prevalent in the archaeal model organisms Sulfolobus acidocaldarius and Haloferax volcanii. We screened for NUDIX hydrolases that could remove the NAD-RNA cap and showed that none of these enzymes removed NAD modifications, but we discovered an enzyme that hydrolyzes ADPR-RNA. We propose that these activities influence the stabilization of NAD and its thermal degradation to potentially toxic ADPR products at elevated growth temperatures.
Intrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and identify a network of regulatory elements that modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2 binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between the PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.
The most basic behavioural states of animals can be described as active or passive. However, while high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which the automated VHF radio-tracking of small vertebrates fitted with lightweight transmitters (< 0.2 g) is used to distinguish between active and passive behavioural states.
A dataset containing > 3 million VHF signals was used to train and test a random forest model in the assignment of either active or passive behaviour to individuals from two forest-dwelling bat species (Myotis bechsteinii (n = 50) and Nyctalus leisleri (n = 20)). The applicability of the model to other taxonomic groups was demonstrated by recording and classifying the behaviour of a tagged bird and by simulating the effect of different types of vertebrate activity with the help of humans carrying transmitters. The random forest model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F-score 0.96–0.98).
The utility of the model in tackling ecologically relevant questions was demonstrated in a study of the differences in the daily activity patterns of the two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that significant differences in the timing of species activity according to ecological preferences or seasonality can be distinguished using our method.
Our approach enables the assignment of VHF signal patterns to fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radio-tracking method, we provide the trained random forest models together with an R-package that includes all necessary data-processing functionalities. In combination with state-of-the-art open-source automated radio-tracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.
Temporal anticipation is a fundamental process underlying complex neural functions such as associative learning, decision-making, and motor-preparation. Here we study event anticipation in its simplest form in human participants using magnetoencephalography. We distributed events in time according to different probability density functions and presented the stimuli separately in two different sensory modalities. We found that the temporal dynamics in right parietal cortex correlate with reaction times to anticipated events. Specifically, after an event occurred, event probability was represented in right parietal activity, hinting at a functional role of event-related potential component P300 in temporal expectancy. The results are consistent across both visual and auditory modalities. The right parietal cortex seems to play a central role in the processing of event probability density. Overall, this work contributes to the understanding of the neural processes involved in the anticipation of events in time.
Using the notion of a root datum of a reductive group G we propose a tropical analogue of a principal G-bundle on a metric graph. We focus on the case G=GLn, i.e. the case of vector bundles. Here we give a characterization of vector bundles in terms of multidivisors and use this description to prove analogues of the Weil--Riemann--Roch theorem and the Narasimhan--Seshadri correspondence. We proceed by studying the process of tropicalization. In particular, we show that the non-Archimedean skeleton of the moduli space of semistable vector bundles on a Tate curve is isomorphic to a certain component of the moduli space of semistable tropical vector bundles on its dual metric graph.
Candida boidinii NAD+-dependent formate dehydrogenase (CbFDH) has gained significant attention for its potential applications in the production of biofuels and various industrial chemicals from inorganic carbon dioxide. The present study reports the atomic X-ray crystal structures of the wild-type CbFDH at cryogenic and ambient temperatures as well as Val120Thr mutant at cryogenic temperature determined at the Turkish Light Source "Turkish DeLight". The structures reveal new hydrogen bonds between Thr120 and water molecules in the mutant CbFDH's active site, suggesting increased stability of the active site and more efficient electron transfer during the reaction. Further experimental data is needed to test these hypotheses. Collectively, our findings provide invaluable insights into future protein engineering efforts that could potentially enhance the efficiency and effectiveness of CbFDH.
Background Overweight and decreased physical fitness are highly prevalent in schizophrenia, represent a major risk factor for cardio-vascular diseases and decrease the patients’ life expectancies. It is thus important to understand the underlying mechanisms that link psychopathology and weight gain. We hypothesize that the dopaminergic reward system plays an important role in this.
Methods: We analyzed the seed-based functional connectivity (FC) of the ventral tegmental area (VTA) in a group of schizophrenic patients (n = 32) and age- as well as gender matched healthy controls (n = 27). We then correlated the resting-state results with physical fitness parameters, obtained in a fitness test, and psychopathology.
Results: The seed-based connectivity analysis revealed decreased functional connections between the VTA and the anterior cingulate cortex (ACC), as well as the dorsolateral prefrontal cortex and increased functional connectivity between the VTA and the middle temporal gyrus in patients compared to healthy controls. The decreased FC between the VTA and the ACC of the patient group could further be associated with increased body fat and negatively correlated with the overall physical fitness. We found no significant correlations with psychopathology.
Conclusion: Although we did not find significant correlations with psychopathology, we could link decreased physical fitness and high body fat with dysconnectivity between the VTA and the ACC in schizophrenia. These findings demonstrate that a dysregulated reward system is not just responsible for symptomatology in schizophrenia but is also involved in comorbidities and could pave the way for future lifestyle therapy interventions.
The COVID-19 pandemic and the associated prevention measures did not only impact on the transmission of COVID-19 but also on the spread of other infectious diseases in an unprecedented natural experiment. Here, we analysed the transmission patterns of 22 different infectious diseases during the COVID-19 pandemic in England. Our results show that the COVID-19 prevention measures generally reduced the spread of pathogens that are transmitted via the air and the faecal-oral route. Moreover, the COVID-19 prevention measures resulted in the sustained suppression of vaccine-preventable infectious diseases also after the removal of restrictions, while non-vaccine preventable diseases displayed a rapid rebound. Despite concerns that a lack of exposure to common pathogens may affect population immunity and result in large outbreaks by various pathogens post-COVID-19, only four of the 22 investigated diseases and disease groups displayed higher post-than pre-pandemic levels without an obvious causative relationship. Notably, this included chickenpox for which an effective vaccine is available but not used in the UK, which provides strong evidence supporting the inclusion of the chickenpox vaccination into the routine vaccination schedule in the UK. In conclusion, our findings provide unique, novel insights into the impact of non-pharmaceutical interventions on the spread of a broad range of infectious diseases.
The NVX-CoV2373-vaccine has recently been licensed, although data on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to dual-dose mRNA-regimens are limited. In this observational study including 66 participants, we show that NVX-CoV2373-induced IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (n=22 each, p=0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. Interestingly, spike-specific CD8 T-cell levels after NVX-CoV2373-vaccination were significantly lower and were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals. However, CD4 T-cell levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFαα and IL-2 (p=0.0007) as compared to mRNA-vaccinated individuals. Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T cells cross-reacted to all tested VOCs from Alpha to Omicron, which may hold promise to protect from severe disease.
Electroencephalography (EEG) has been used for decades to identify neurocognitive processes related to intelligence. Evidence is accumulating for associations with neural markers of higher-order cognitive processes (e.g., working memory); however, whether associations are specific to complex processes or also relate to earlier processing stages remains unclear. Addressing these issues has implications for improving our understanding of intelligence and its neural correlates. The mismatch negativity (MMN) is an event-related brain potential (ERP) that is elicited when, within a series of frequent standard stimuli, rare deviant stimuli are presented. As stimuli are typically presented outside the focus of attention, the MMN is suggested to capture automatic pre-attentive discrimination processes. However, the MMN and its relation to intelligence has largely only been studied in the auditory domain, thus preventing conclusions about the involvement of automatic discrimination processes in humans’ dominant sensory modality vision. Electroencephalography was recorded from 50 healthy participants during a passive visual oddball task that presented simple sequence violations as well as deviations within a more complex hidden pattern. Signed area amplitudes and fractional area latencies of the visual mismatch negativity (vMMN) were calculated with and without Laplacian transformation. Correlations between vMMN and intelligence (Raven’s Advanced Progressive Matrices) were of negligible to small effect sizes, differed critically between measurement approaches, and Bayes Factors provided anecdotal to substantial evidence for the absence of an association. We discuss differences between the auditory and visual MMN, the implications of different measurement approaches, and offer recommendations for further research in this evolving field.
Effective spectral functions of the ρ meson are reconstructed by considering the lifetimes inside different media using the hadronic transport SMASH (Simulating Many Accelerated Strongly-interacting Hadrons). Due to inelastic scatterings, resonance lifetimes are dynamically shortened (collisional broadening), even though the employed approach assumes vacuum resonance properties. Analyzing the ρ meson lifetimes allows to quantify an effective broadening of the decay width and spectral function, which is important in order to distinguish dynamical effects from additional genuine medium modifications to the spectral functions, indicating e.g. an onset of chiral symmetry restoration. The broadening of the spectral function in a thermalized system is shown to be consistent with other theoretical calculations. The effective ρ meson spectral function is also presented for the dynamical evolution of heavy-ion collisions, finding a clear correlation of the broadening to system size, which is explained by an observed dependence of the width on the local hadron density. Furthermore, the difference in the results between the thermal system and full collision dynamics is explored, which may point to non-equilibrium effects.
Reactive oxygen species (ROS) are constant by-products of aerobic life. In excess, ROS lead to cytotoxic protein aggregates, which are a hallmark of ageing in animals and linked to age-related pathologies in humans. Acylamino acid-releasing enzymes (AARE) are bifunctional serine proteases, acting on oxidized proteins. AARE are found in all domains of life, albeit under different names, such as acylpeptide hydrolase (APEH/ACPH), acylaminoacyl peptidase (AAP), or oxidized protein hydrolase (OPH). In humans, AARE malfunction is associated with age-related pathologies, while their function in plants is less clear. Here, we provide a detailed analysis of AARE genes in the plant lineage and an in-depth analysis of AARE localization and function in the moss Physcomitrella and the angiosperm Arabidopsis. AARE loss-of-function mutants have not been described for any organism so far. We generated and analysed such mutants and describe a connection between AARE function, aggregation of oxidized proteins and plant ageing, including accelerated developmental progression and reduced life span. Our findings complement similar findings in animals and humans, and support a unified concept of ageing.