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High-resolution mapping of cell cycle dynamics during T-cell development and regeneration in vivo
(2024)
Control of cell proliferation is critical for the lymphocyte life cycle. However, little is known on how stage-specific alterations in cell cycle behavior drive proliferation dynamics during T-cell development. Here, we employed in vivo dual-nucleoside pulse labeling combined with determination of DNA replication over time as well as fluorescent ubiquitination-based cell cycle indicator mice to establish a quantitative high-resolution map of cell cycle kinetics of thymocytes. We developed an agent-based mathematical model of T-cell developmental dynamics. To generate the capacity for proliferative bursts, cell cycle acceleration followed a ‘stretch model’, characterized by simultaneous and proportional contraction of both G1 and S phase. Analysis of cell cycle phase dynamics during regeneration showed tailored adjustments of cell cycle phase dynamics. Taken together, our results highlight intrathymic cell cycle regulation as an adjustable system to maintain physiologic tissue homeostasis and foster our understanding of dysregulation of the T-cell developmental program.
Agility, as the ability to react rapidly to unforeseen events, is an essential component of football performance. However, existing agility diagnostics often do not reflect the complex motor–cognitive interaction required on the field. Therefore, this study evaluates the criterion and ecological validity of a newly developed motor–cognitive dual-task agility approach in elite youth football players and compare it to a traditional reactive agility test. Twenty-one male youth elite football players (age:17.4 ±0 .6; BMI:23.2 ± 1.8) performed two agility tests (reactive agility, reactive agility with integrated multiple-object-tracking (Dual-Task Agility)) on the SKILLCOURT system. Performance was correlated to motor (sprint, jump), cognitive (executive functions, attention, reaction speed) and football specific tests (Loughborough soccer passing test (LSPT)) as well as indirect game metrics (coaches' rating, playing time). Reactive agility performance showed moderate correlations to attention and choice reaction times (r = 0.48−0.63), as well as to the LSPT (r = 0.51). The dual-task agility test revealed moderate relationships with attention and reaction speed (r = 0.47−0.58), executive functions (r = 0.45−0.63), as well as the game metrics (r = 0.51−0.61). Finally, the dual-task agility test significantly differentiated players based on their coaches' rating and playing time using a median split (p < 0.05; d = 0.8–1.28). Motor–cognitive agility performance in elite youth football players seems to be primarily determined by cognitive functions. The integration of multiple object tracking into reactive agility testing seems to be an ecologically valid approach for performance diagnostics in youth football.
Highlights
* The study introduces a novel motor–cognitive dual-task agility approach (incorporation of multiple-object-tracking in agility testing), evaluating its criterion and ecological validity in elite youth football players compared to a standard agility test.
* The standard agility test was shown to have moderate correlations with attention and choice reaction times, while the dual-task agility approach additionally incorporates executive functions
* While the agility test correlates to football-specific test performance, the dual-task agility test significantly discriminates players based on their potential ratings and in-season playing time, highlighting its potential as a valuable tool for assessing performance in youth football.
* The findings suggest that agility performance in elite youth football is primarily determined by cognitive functions
* Incorporating more complex cognitive elements such as multiple-object-tracking in agility testing may improve ecological validity and therefore the predictive value of the testing procedure.
Using electron-positron annihilation data samples corresponding to an integrated luminosity of 4.5 fb−1, collected by the BESIII detector in the energy region between 4600 MeV and 4699 MeV, we report the first observations of the Cabibbo-suppressed decays Λ+c→nπ+π0, Λ+c→nπ+π−π+, and the Cabibbo-favored decay Λ+c→nK−π+π+ with statistical significances of 7.9σ, 7.8σ, and >10σ, respectively. The branching fractions of these decays are measured to be B(Λ+c→nπ+π0)=(0.64±0.09±0.02)%, B(Λ+c→nπ+π−π+)=(0.45±0.07±0.03)%, and B(Λ+c→nK−π+π+)=(1.90±0.08±0.09)%, where the first uncertainties are statistical and the second are systematic. We find that the branching fraction of the decay Λ+c→nπ+π0 is about one order of magnitude higher than that of Λ+c→nπ+.
The energy-dependent cross section for e+e−→ηψ(2S) is measured at eighteen center of mass energies from 4.288 GeV to 4.951 GeV using the BESIII detector. Using the same data samples, we also perform the first search for the reaction e+e−→ηX~(3872), but no evidence is found for the X~(3872) in the π+π−J/ψ mass distribution. At each of the eighteen center of mass energies, upper limits at the 90\% confidence level on the cross section for e+e−→ηψ(2S) and on the product of the e+e−→ηX~(3872) cross section with the branching fraction of X~(3872)→π+π−J/ψ are reported.
The main goal of this work is to contribute to the existing knowledge of soil micro-fungi in Panama and Germany. Studies about soil degradation and its influents in the soil fungi diversity have not been investigated as extensively in these countries. This is an extensive and challenging topic to examine since there is an immense phenotypic and genetic diversity in the soil fungal community and relating this community together with factors of soil degradation is an extensive task. For this reason, the present thesis studies the species identified in the study areas, in other words, the soil fungal diversity in relation to environmental factors in the Taunus Mountain range in Frankfurt, Germany, and in the Majagua valley in Chiriquí, Panama. Two complementary objectives were achieved, the first was the development of a theoretical irrigation model for degraded soils. The second was the development of a mobile application to facilitate laboratory work in the cultivation of soil micro-fungi.
The design of the methodology was based on identifying the species and relating the diversity found to soil factors. Soil samples were taken in both countries: the Taunus Mountain range was sampled eight times from January to November 2012 and the Majagua valley was sampled on three occasions between February and July 2012. In both studies, the areas included three different vegetation types (forest, grassland, and bare soil). Samples were separated for two purposes: the assessment of fungal diversity by molecular and morphological methods and soil characterization.
Soil samples used in the methodology of pyrosequencing were related to global climatic factors. Morphological identification was achieved with identification keys. Micro-fungi were cultivated in different media until obtaining pure cultures. Molecular identification was performed by getting the DNA sequences using the ITS1 and ITS4 primers and comparing the sequences with other reference sequences from GenBank. This was done considering the BLAST algorithm, which considered sequences that matched 98 % or more of maximum identity as reliable identifications.
Soil characterization was carried out to measure the soil's Physico-chemical properties; those abiotic factors were compaction, temperature, pH, moisture, and soil composition.
Species richness was calculated in each study area with the estimators Chao, Jackknife, and Bootstrap. Furthermore, the species accumulation curves were performed to observe the species discovery rate and estimate sample completeness. Estimate linear regression models correlated the influence between the soil factors (temperature, moisture, pH, soil compaction, and soil composition) and the species richness. In the same way, an analysis of ecological distance was undertaken based on the similarity in the species composition, compared across samples, and correlated with soil factors, using non-metric multidimensional scaling (NMDs).
Study of abundance showed differences between the bare soil abundances and the forest abundances in Germany and Panama; the grasslands in both countries work as transitional areas in the fungi abundance. The key stone species in Germany were Penicillium daleae, and Pochonia bulbillosa, whereas in Panama were Purpureocillium lilacinum and Trichoderma harzianum. Based on Pareto analysis, a theoretical irrigation model was developed to counteract the degradation effects on the abundance of micro-fungi in the soil.
Applications for mobile devices dealing with the cultivation of soil micro fungi were sought. Due to the small number of existing applications, a new App called Soil-Fungi-Cultures (SFC) was developed to facilitate data collection of cultivated soil micro fungi. App Inventor was the program used to design, program, test, and publish the application developed. The developed application was compared with other applications used in identifying bacteria cultures. The results showed that the new application needed more time to capture the records because it saves more information, the navigation flow was acceptable, the number of clicks was high, but it is due to the usefulness in data capture, and finally, the users rated it as a good application with an eight out of ten rating.
Pyrosequencing resulted in 204 Operational Taxonomic Units (OTUs) considering the two study areas (the Taunus Mountain range and the Majagua valley). The Pyrosequencing database was used to contribute to the most important study of fungal diversity globally based on OTUs, which surpasses any study of molecular and taxonomic diversity previously conducted. The principal result in this study was that the climatic factor is the best predictor of fungal richness and community composition on a global scale. However, the part of the research that focused on the local scale, that is to say, on the correlation patterns between the distribution of fungal species and abiotic factors, showed that the soil properties and degradation levels were not associated with fungal richness, diversity or soil composition in the study areas in Germany or Panama. The above confirms that there are exceptions to the way relationships between soil factors with fungal diversity are established at the local level.
In the case of soil samples used for morphological identification, 71 fungal species were obtained, 47 from Germany, and 32 from Panama.
The expanding field of epitranscriptomics might rival the epigenome in the diversity of biological processes impacted. In recent years, the development of new high-throughput experimental and computational techniques has been a key driving force in discovering the properties of RNA modifications. Machine learning applications, such as for classification, clustering or de novo identification, have been critical in these advances. Nonetheless, various challenges remain before the full potential of machine learning for epitranscriptomics can be leveraged. In this review, we provide a comprehensive survey of machine learning methods to detect RNA modifications using diverse input data sources. We describe strategies to train and test machine learning methods and to encode and interpret features that are relevant for epitranscriptomics. Finally, we identify some of the current challenges and open questions about RNA modification analysis, including the ambiguity in predicting RNA modifications in transcript isoforms or in single nucleotides, or the lack of complete ground truth sets to test RNA modifications. We believe this review will inspire and benefit the rapidly developing field of epitranscriptomics in addressing the current limitations through the effective use of machine learning.
Based on electron positron collision data collected with the BESIII detector operating at the BEPCII storage rings, the differential cross sections of inclusive π0 and K0S production as a function of hadron momentum, normalized by the total cross section of the e+e−→ hadrons process, are measured at six center-of-mass energies from 2.2324 to 3.6710 GeV. Our results with a relative hadron energy coverage from 0.1 to 0.9 significantly deviate from several theoretical calculations based on existing fragmentation functions, especially at lower energies.
Using 7.93 fb−1 of e+e− collision data collected at the center-of-mass energy of 3.773 GeV with the BESIII detector, we measure the absolute branching fractions of D0→K−e+νe, D0→K−μ+νμ, D+→K¯0e+νe, and D+→K¯0μ+νμ to be (3.509±0.009stat.±0.013syst.)%, (3.408±0.011stat.±0.013syst.)%, (8.856±0.039stat.±0.078syst.)%, and (8.661±0.046stat.±0.080syst.)%, respectively. By performing a simultaneous fit to the partial decay rates of these four decays, the product of the hadronic form factor fK+(0) and the modulus of the c→s CKM matrix element |Vcs| is determined to be fK+(0)|Vcs|=0.7162±0.0011stat.±0.0012syst.. Taking the value of |Vcs|=0.97349±0.00016 from the standard model global fit or that of fK+(0)=0.7452±0.0031 from the LQCD calculation as input, we derive the results fK+(0)=0.7357±0.0011stat.±0.0012syst. and |Vcs|=0.9611±0.0015stat.±0.0016syst.±0.0040LQCD.
The decay 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is searched for through the radiative transition 𝜓(3686)→𝛾𝜂𝑐(2𝑆) using 448 million 𝜓(3686) events accumulated at the BESIII detector. The first evidence of 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is found with a statistical significance of 3.5𝜎. The product of the branching fractions of 𝜓(3686)→𝛾𝜂𝑐(2𝑆) and 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is measured to be Br(𝜓(3686)→𝛾𝜂𝑐(2𝑆))×Br(𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂)=(2.97±0.81±0.26)×10−6, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is determined to be Br(𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂)=(42.4±11.6±3.8±30.3)×10−4, where the third uncertainty is transferred from the uncertainty of the branching fraction of 𝜓(3686)→𝛾𝜂𝑐(2𝑆).
The decay $\eta_c(2S)\to\pipieta$ is searched for through the radiative transition ψ(3686)→γηc(2S) using 448 million ψ(3686) events accumulated at the BESIII detector. The first evidence of ηc(2S)→π+π−η is found with a statistical significance of 3.5σ. The product of the branching fractions of ψ(3686)→γηc(2S) and $\eta_c(2S)\to\pipieta$ is measured to be $Br(\psi(3686)\to\gamma\eta_c(2S))\times Br(\eta_c(2S)\to\pipieta)=(2.97\pm0.81\pm0.26)\times10^{-6}$, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay $\eta_c(2S)\to\pipieta$ is determined to be $Br(\eta_c(2S)\to\pipieta)=(42.4\pm11.6\pm3.8\pm30.3)\times10^{-4}$, where the third uncertainty is transferred from the uncertainty of the branching fraction of ψ(3686)→γηc(2S).
The decay $\eta_c(2S)\to\pipieta$ is searched for through the radiative transition ψ(3686)→γηc(2S) using 448 million ψ(3686) events accumulated at the BESIII detector. The first evidence of ηc(2S)→π+π−η is found with a statistical significance of 3.5σ. The product of the branching fractions of ψ(3686)→γηc(2S) and $\eta_c(2S)\to\pipieta$ is measured to be $Br(\psi(3686)\to\gamma\eta_c(2S))\times Br(\eta_c(2S)\to\pipieta)=(2.97\pm0.81\pm0.26)\times10^{-6}$, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay $\eta_c(2S)\to\pipieta$ is determined to be $Br(\eta_c(2S)\to\pipieta)=(42.4\pm11.6\pm3.8\pm30.3)\times10^{-4}$, where the third uncertainty is transferred from the uncertainty of the branching fraction of ψ(3686)→γηc(2S).
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000~GeV. Using a fully differential angular description of the final state particles, the complete information of the Σ+ electromagnetic form factors in the time-like region is extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat.)~±~0.18~(syst.) at s√ = 2.3960~GeV, ΔΦ = 55∘~±~19∘~(stat.) ±~14∘~(syst.) at s√ = 2.6454~GeV, and 78∘~±~22∘~(stat.) ±~9∘~(syst.) at s√ = 2.9000~GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000~GeV. Using a fully differential angular description of the final state particles, the complete information of the Σ+ electromagnetic form factors in the time-like region is extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat.)~±~0.18~(syst.) at s√ = 2.3960~GeV, ΔΦ = 55∘~±~19∘~(stat.) ±~14∘~(syst.) at s√ = 2.6454~GeV, and 78∘~±~22∘~(stat.) ±~9∘~(syst.) at s√ = 2.9000~GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000 GeV. Using a fully differential angular description of the final state particles, both the relative magnitude and phase information of the Σ+ electromagnetic form factors in the timelike region are extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat)~±~0.18~(syst) at s√ = 2.3960 GeV, ΔΦ = 55∘~±~19∘~(stat) ±~14∘~(syst) at s√ = 2.6454 GeV, and 78∘~±~22∘~(stat) ±~9∘~(syst) at s√ = 2.9000 GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Using a data sample of (10087±44)×106 J/ψ events collected by the BESIII detector in 2009, 2012, 2018 and 2019, the electromagnetic Dalitz process J/ψ→e+e−η(1405) is observed via the decay η(1405)→π0f0(980), f0(980)→π+π−, with a significance of about 9.6σ. The branching fraction of this decay is measured to be B(J/ψ→e+e−π0η(1405)→e+e−π0f0(980)→e+e−π0π+π−)=(2.02±0.24(stat.)±0.09(syst.))×10−7. The branching-fraction ratio B(J/ψ→e+e−η(1405))/B(J/ψ→γη(1405)) is determined to be (1.35±0.19(stat.)±0.06(syst.))×10−2. Furthermore, an e+e− invariant-mass dependent transition form factor of J/ψ→e+e−η(1405) is presented for the first time. The obtained result provides input for different theoretical models, and is valuable for the improved understanding the intrinsic structure of the η(1405) meson.
The high collision energies reached at the LHC lead to significant production yields of light (anti)hypernuclei in proton–proton (pp), proton–lead (p–Pb) and, in particular, Pb–Pb collisions. The lightest known hypernucleus is the hypertriton, which is a bound state of a proton, a neutron, and a Λ hyperon. It decays weakly with a decay length of a few centimeters. The excellent tracking and particle identification capabilities of the ALICE detector, exploiting the energy loss measurement of the Time Projection Chamber (TPC) and using the Inner Tracking System (ITS) to distinguish between primary and secondary (decay) vertices, allow for the determination of the hypertriton yield across different collision systems, its lifetime, and its binding energy. The latest hypertriton lifetime measurement in Pb–Pb collisions performed in the 2-body decay channel will be presented. This measurement contributes to the solution of the hypertriton lifetime puzzle. In addition, the hypertriton production in different collision systems and at different energies will be compared to model predictions. Due to its low binding energy, and hence to its large size, the hypertriton is the ideal candidate to distinguish between statistical hadronization and coalescence models. With the precision of the presented yield measurements some variants of the aforementioned models can be excluded.
Introduction: Due to an inhibited tryptophan resorption, patients with fructose malabsorption are expected to experience decreased serotonin synthesis. A deficiency of serotonin may cause internalizing mental disorders like depression and anxiety, and a fructose-oriented eating behavior may affect these symptoms.
Methods: The parents of 24 children and adolescents with a currently diagnosed fructose malabsorption aged 4;00–13;02 years (M = 8.10, SD = 2.05), the parents of 12 patients with a currently confirmed combination of fructose and lactose malabsorption aged 4;00–12;11 years (M = 8.07, SD = 2.11) and the parents of a comparative sample of 19 healthy participants aged 5;00 to 17;07 years (M = 9.06, SD = 3.04) were interviewed. The interviews were conducted using a screening questionnaire of the German “Diagnostic System of Mental Disorders in children and adolescents based on the ICD-10 and DSM-5 DISYPS-III” and a self-developed questionnaire on eating, leisure and sleeping behavior.
Results: On standardized scales parents of children with fructose malabsorption reported higher levels of Depression compared to symptoms of Attention-Deficit/Hyperactivity Disorders (ADHD) and Oppositional Defiant and Conduct Disorders (ODD/CD). Compared to healthy controls, for patients with fructose malabsorption, higher symptom levels of Depression and Anxiety were reported. With regard to eating behavior, within the group with a combination of fructose and lactose malabsorption, a strong positive association between an increased fruit sugar consumption and higher levels of Anxiety and Obsessive-Compulsive Disorders/Tics were found.
Discussion: These results suggest a close association between fructose malabsorption and elevated internalizing psychological symptoms in children and adolescents.
Clinical trial registration: https://drks.de/search/en/trial/DRKS00031047, DRKS-ID [DRKS00031047].
Based on 4.4 fb−1 of e+e− annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure \textit{W}-boson-exchange decay Λ+c→Ξ0K+ is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be αΞ0K+=0.01±0.16(stat.)±0.03(syst.). This result reflects the non-interference effect between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes has two solutions, which are δp−δs=−1.55±0.25(stat.)±0.05(syst.) rad or 1.59±0.25(stat.)±0.05(syst.) rad.
Based on 4.4 fb−1 of e+e− annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-exchange decay Λ+c→Ξ0K+ is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be αΞ0K+=0.01±0.16(stat.)±0.03(syst.). This result reflects the interference between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes is δp−δs=−1.55±0.25(stat.)±0.05(syst.) rad.
Based on 4.4 fb−1 of e+e− annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-exchange decay Λ+c→Ξ0K+ is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be αΞ0K+=0.01±0.16(stat.)±0.03(syst.). This result reflects the interference between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes is δp−δs=−1.55±0.25(stat.)±0.05(syst.) rad.
Based on 4.4 fb−1 of e+e− annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure \textit{W}-boson-exchange decay Λ+c→Ξ0K+ is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be αΞ0K+=0.01±0.16(stat.)±0.03(syst.). This result reflects the non-interference effect between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes has two solutions, which are δp−δs=−1.55±0.25(stat.)±0.05(syst.) rad or 1.59±0.25(stat.)±0.05(syst.) rad.
Based on 4.4 fb−1 of e+e− annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-exchange decay Λ+c→Ξ0K+ is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be αΞ0K+=0.01±0.16(stat.)±0.03(syst.). This result reflects the interference between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes is δp−δs=−1.55±0.25(stat.)±0.05(syst.) rad.
Based on electron positron collision data collected with the BESIII detector operating at the BEPCII storage rings, the differential cross sections of inclusive π0 and K0S production as a function of hadron momentum, normalized by the total cross section of the e+e−→ hadrons process, are measured at six center-of-mass energies from 2.2324 to 3.6710 GeV. Our results with a relative hadron energy coverage from 0.1 to 0.9 significantly deviate from several theoretical calculations based on existing fragmentation functions, especially at lower energies.
Based on electron positron collision data collected with the BESIII detector operating at the BEPCII storage rings, the differential cross sections of inclusive π0 and K0S production as a function of hadron momentum, normalized by the total cross section of the e+e−→ hadrons process, are measured at six center-of-mass energies from 2.2324 to 3.6710 GeV. Our results with a relative hadron energy coverage from 0.1 to 0.9 significantly deviate from several theoretical calculations based on existing fragmentation functions, especially at lower energies.
Dendritic spines are small membranous protrusions covering the dendritic tree of principal telencephalic neurons, such as the GC or CA2-pc. The CA2-subregion is crucial for social memory. Dendritic spines are a main site of synaptic plasticity, which is a key element of learning and memory. The plasticity-related protein Synaptopodin (SP) is essential to form the spine apparatus (SA), a spine-specific organelle involved in synaptic plasticity. SP stabilizes dendritic spines. This thesis investigated, for the first time, the dendritic SP-distribution and its influence on spine density and spine head size under different conditions in adult mice ex vivo: 1) SP-overexpression (gain-of-function), 2) SP-deficiency (loss-of-function), and 3) wild type-level of SP-expression in male and female mice (sex-differences in dCA2). SP-overexpression in adult male CSPtg-mice led to a ~doubled ratio of SP+ spines in the OML of the DG, while the spine density, the average spine head size and the average SP-puncta size were not affected. Consistently, SP-deficiency in adult male SP-KO animals had no significant effect on average spine head size. Of importance, under SP-overexpression, many small spines and a few large spines become SP+, assumingly assembling a SA. On a functional level, this may indicate an activation of silent synapses. dCA2 showed sex specific differences in spine density and spine morphology in a layer-specific manner: In males, pc-spines of the basal dCA2-compartment showed larger spine heads than females in the diestrus stage of their cycle (females (diestrus), while spine density was not significantly different. In the apical dCA2-compartment (sr), females (diestrus) showed an increased spine density, while spine head size was still shifted towards larger head sizes in males. In addition, dCA2 showed significant layer-specific differences in spine head size, but in a sex-independent manner: In both sexes, average spine head size in the apical sr was significantly smaller than in the basal so. This findings could reflect a yet unknown compartment-specific difference in synaptic plasticity in the basal compartment, which is preferentially targeted by neuromodulatory input from extrahippocampal sources such as the PVN or SUM99,101,170,189-195. In so of dCA2, there was no sex-specific difference in SP-puncta size or in the ratio of SP+ spines, indicating that SP is distributed in a sex-independent manner in dCA2 in adult mice.
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 suggest a unified concept of ageing may exist in different life forms.
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 suggest a unified concept of ageing may exist in different life forms.
Protein oxidation results from the reaction of amino-acid side chains with reactive oxygen species (ROS) and is partly irreversible. In non-photosynthetic tissues, mitochondria are a main source of ROS, whereas plastids are the major source in photosynthetic tissues. Oxidized proteins suffer from decreased structural integrity and even loss of function, and their accumulation leads to cytotoxic aggregates. In mammals, aggregate formation correlates with aging and is linked to several age-related pathologies. Mammalian proteolytic pathways for clearance of oxidized proteins are under intensive research, while mechanistic insights into this process in plants is scarce. Acylamino acid-releasing (AARE) enzymes are ATP-independent serine proteases, presumably acting on oxidized proteins and operating in a dual exo-/endopeptidase mode. They are found in all domains of life. Here, we investigated AARE enzymes in the moss Physcomitrella and the angiosperm Arabidopsis and identified three homologous nuclear genes in Physcomitrella (PpAARE1-3) and a single nuclear gene in Arabidopsis (AtAARE). Surprisingly, we observed triple localization of the proteins AtAARE and PpAARE1 to plastids, mitochondria and the cytosol in vivo, likely conserved across the plant lineage. This represents an ATP-independent possibility for degradation of oxidized proteins in the major source organelles of ROS in plants, which is distinct to mammals. Combinatorial knockout plants and protein interaction analysis revealed specific interactions of the moss AARE isoforms and functions in progressive aging. Analysis of an AtAARE T-DNA mutant further suggests the evolutionary conservation of AARE function in age-related development.
RNA modification is a dynamic and complex process that involves the addition of various chemical groups to RNA molecules, contributing to their diversity and functional complexity. Among all the RNA modifications, N6-methyladenosine (m6A) is the most common post-transcriptional modification found in mRNA molecules, particularly in eukaryotic mRNA. It involves methylation of the adenosine base at the nitrogen-6 position. This modification plays a crucial role in many aspects of RNA metabolism, including splicing, stability, translation, and the cellular response to stress. With the development of m6A sequencing technologies, our knowledge of m6A has evolved rapidly over the past two decades. However, one of the most widely used m6A profiling techniques termed “m6A individual-nucleotide resolution UV cross-linking and immunoprecipitation (miCLIP)” suffers from a high unspecific background signal due to the limited antibody binding specificity.
To accurately discriminate m6A sites from the background signal in miCLIP data, in Chapter 4, I first developed different strategies to identify the true miCLIP2 signal changes that are corrected for the underlying transcript abundance changes. I performed this analysis on data that generated with an improved experiment protocol, named miCLIP2. With the best performing strategy, the Bin-based method, I detected more than 10,000 genuine m6A sites. I then used the information embedded in the genuine m6A sites to train a machine learning model - named "m6Aboost" - to enable accurate m6A site detection from the miCLIP2 data without a control dataset from an m6A depletion cell line. To allow an easy access for future users, I packaged the m6Aboost model into an R package that is available on Bioconductor.
Although previous studies have reported that m6A is involved in three different RNA decay pathways, it remains unclear how a pathway is selected for a specific transcript or m6A site. In Chapter 5, I reveal that m6A sites in the coding sequence (CDS) induce a stronger and faster RNA decay than the m6A sites in the 3’ untranslated region (3’UTR). Through an in-depth investigation, I found that m6A sites in CDS trigger a novel mRNA decay pathway, which I termed CDS-m6A decay (CMD). Importantly, CMD is distinct from the three previously reported m6A-mediated decay pathways. In terms of its mechanism, CMD relies on translation, where m6A sites in the CDS lead to ribosome pausing and subsequent destabilization of the transcript. The transcripts targeted by CMD are identified by the m6A reader protein YTHDF2, preferentially localized to processing bodies (P-bodies), and undergo degradation facilitated by the decapping factor DCP2. CMD provides a flexible way to control the expression of CDS m6A-containing transcripts which include many developmental regulators and retrogenes.
In summary, this PhD thesis introduces a novel workflow for identifying m6A sites in miCLIP data through the implementation of the m6Aboost machine learning model. Using the m6A sites identified by m6Aboost and additional data, a newly uncovered m6A-mediated mRNA decay pathway, CMD, is elucidated, providing valuable insights into m6A-mediated decay processes.
We study the direct production of the JPC=1++ charmonium state χc1(1P) in electron-positron annihilation by carrying out an energy scan around the mass of the χc1(1P). The data were collected with the BESIII detector at the BEPCII collider. An interference pattern between the signal process e+e−→χc1(1P)→γJ/ψ→γμ+μ− and the background processes e+e−→γISRJ/ψ→γISRμ+μ− and e+e−→γISRμ+μ− are observed by combining all the data samples. The χc1(1P) signal is observed with a significance of 5.1σ. This is the first observation of a C-even state directly produced in e+e− annihilation. The electronic width of the χc1(1P) resonance is determined to be Γee=(0.12+0.13−0.08) eV, which is of the same order of magnitude as theoretical calculations.
We study the direct production of the JPC=1++ charmonium state χc1(1P) in electron-positron annihilation by carrying out an energy scan around the mass of the χc1(1P). The data were collected with the BESIII detector at the BEPCII collider. An interference pattern between the signal process e+e−→χc1(1P)→γJ/ψ→γμ+μ− and the background processes e+e−→γISRJ/ψ→γISRμ+μ− and e+e−→γISRμ+μ− are observed by combining all the data samples. The χc1(1P) signal is observed with a significance of 5.1σ. This is the first observation of a C-even state directly produced in e+e− annihilation. The electronic width of the χc1(1P) resonance is determined to be Γee=(0.12+0.13−0.08) eV, which is of the same order of magnitude as theoretical calculations.
We study the direct production of the JPC=1++ charmonium state χc1(1P) in electron-positron annihilation by carrying out an energy scan around the mass of the χc1(1P). The data was collected with the BESIII detector at the BEPCII collider. An interference pattern between the signal process e+e−→χc1(1P)→γJ/ψ→γμ+μ− and the background processes e+e−→γISRJ/ψ→γISRμ+μ− and e+e−→γISRμ+μ− is observed by combining all the data samples. The χc1(1P) signal is observed with a significance of 5.1σ. This is the first observation of a C-even state directly produced in e+e− annihilation. The electronic width of the χc1(1P) resonance is determined to be Γee=(0.12+0.13−0.08) eV, which is of the same order of magnitude as theoretical calculations.
Based on 10 billion J/ψ events collected at the BESIII experiment, a search for CP violation in Λ decay is performed in the difference between CP-odd decay parameters α− for Λ→pπ− and α+ for Λ¯→p¯π+ by using the process e+e−→J/ψ→ΛΛ¯. With a five-dimensional fit to the full angular distributions of the daughter baryon, the most precise values for the decay parameters are determined to be α−=0.7519±0.0036±0.0024 and α+=−0.7559±0.0036±0.0030, respectively. The Λ and Λ¯ averaged value of the decay parameter is extracted to be αavg=0.7542±0.0010±0.0024 with unprecedented accuracy. The CP asymmetry ACP=(α−+α+)/(α−−α+) is determined to be −0.0025 ± 0.0046 ± 0.0012, which is one of the most precise measurements in the baryon sector. The reported results for the decay parameter will play an important role in the studies of the polarizations and CP violations for the strange, charmed and beauty baryons.
The absolute branching fraction of the decay Λc(2625)+→Λ+cπ+π− is measured for the first time to be (50.7±5.0stat.±4.9syst.)% with 368.48 pb−1 of e+e− collision data collected by the BESIII detector at the center-of-mass energies of s√=4.918 and 4.950 GeV. This result is lower than the naive prediction of 67\%, obtained from isospin symmetry, by more than 2σ, thereby indicating that the novel mechanism referred to as the \textit{threshold effect}, proposed for the strong decays of Λc(2595)+, also applies to Λc(2625)+. This measurement is necessary to obtain the coupling constants for the transitions between s-wave and p-wave charmed baryons in heavy hadron chiral perturbation theory. In addition, we search for the decay Λc(2595)+→Λ+cπ+π−. No significant signal is observed, and the upper limit on its branching fraction is determined to be 80.8\% at the 90\% confidence level.
In this Letter, a systematic study of the weak radiative hyperon decay Ξ0→Λγ at an electron-positron collider using entangled Ξ0Ξ¯0 pair events is presented. The absolute branching fraction for this decay has been measured for the first time, and is (1.347±0.066stat.±0.054syst.)×10−3. The decay asymmetry parameter, which characterizes the effect of parity violation in the decay, is determined to be −0.741±0.062stat.±0.019syst.. The obtained results are consistent with the world average values within the uncertainties, offering valuable insights into the underlying mechanism governing the weak radiative hyperon decays. The charge conjugation parity (CP) symmetries of branching fraction and decay asymmetry parameter in the decay are also studied. No statistically significant violation of charge conjugation parity symmetry is observed.
In this Letter, a systematic study of the weak radiative hyperon decay Ξ0→Λγ at an electron-positron collider using entangled Ξ0Ξ¯0 pair events is presented. The absolute branching fraction for this decay has been measured for the first time, and is (1.347±0.066stat.±0.054syst.)×10−3. The decay asymmetry parameter, which characterizes the effect of parity violation in the decay, is determined to be −0.741±0.062stat.±0.019syst.. The obtained results are consistent with the world average values within the uncertainties, offering valuable insights into the underlying mechanism governing the weak radiative hyperon decays. The charge conjugation parity (CP) symmetries of branching fraction and decay asymmetry parameter in the decay are also studied. No statistically significant violation of charge conjugation parity symmetry is observed.
Model-independent determination of the strong-phase difference between D⁰ and D̄⁰ → π⁺π⁻π⁺π⁻ decays
(2024)
Measurements of the strong-phase difference between D0 and D¯0→π+π−π+π− are performed in bins of phase space. The study exploits a sample of quantum-correlated DD¯ mesons collected by the BESIII experiment in e+e− collisions at a center-of-mass energy of 3.773~GeV, corresponding to an integrated luminosity of 2.93~fb−1. Here, D denotes a neutral charm meson in a superposition of flavor eigenstates. The reported results are valuable for measurements of the CP-violating phase γ (also denoted ϕ3) in B±→DK±, D→π+π−π+π− decays, and the binning schemes are designed to provide good statistical sensitivity to this parameter. The expected uncertainty on γ arising from the precision of the strong-phase measurements, when applied to very large samples of B-meson decays, is around 1.5∘ or 2∘, depending on the binning scheme. The binned strong-phase parameters are combined to give a value of F4π+=0.746±0.010±0.004 for the CP-even fraction of D0→π+π−π+π− decays, which is around 30\% more precise than the previous best measurement of this quantity.
Using (2712.4±14.3)×106 ψ(3686) events collected with the BESIII detector operating at the BEPCII collider, we search for the hadronic transition hc→π+π−J/ψ via ψ(3686)→π0hc. No significant signal is observed. We set the most stringent upper limits to date on the branching fractions B(ψ(3686)→π0hc)×B(hc→π+π−J/ψ) and B(hc→π+π−J/ψ) at the 90% confidence level, which are determined to be 6.7×10−7 and 9.4×10−4, respectively.
The hippocampus (HPC) supports spatial working memory (SWM) through its interactions with the prefrontal cortex (PFC). However, it is not clear whether and how the dorsal (dHPC) and ventral (vHPC) poles of the HPC make distinct contributions to SWM and whether they differentially influence the PFC. To address this question, we optogenetically silenced the dHPC or the vHPC while simultaneously recording from the PFC of mice performing a SWM task. We found that whereas both HPC subregions were necessary during the encoding phase of the task, only the dHPC was necessary during the choice phase. Silencing of either subregion altered the spatial firing patterns of PFC neurons. However, only silencing of the vHPC affected their coding of spatial goals. These results thus reveal distinct contributions of the dorsal and ventral HPC poles to SWM and the coding of behaviorally-relevant spatial information by PFC neurons.
LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.
Light axion fields, if they exist, can be sourced by neutron stars due to their coupling to nuclear matter, and play a role in binary neutron star mergers. We report on a search for such axions by analyzing the gravitational waves from the binary neutron star inspiral GW170817. We find no evidence of axions in the sampled parameter space. The null result allows us to impose constraints on axions with masses below 10−11 eV by excluding the ones with decay constants ranging from 1.6×1016 to 1018 GeV at a 3𝜎 confidence level. Our analysis provides the first constraints on axions from neutron star inspirals, and rules out a large region in parameter space that has not been probed by the existing experiments.
Inspirals of an intermediate mass black hole (IMBH) and a solar mass type object will be observable by space based gravitational wave detectors such as the Laser Interferometer Space Antenna. A dark matter overdensity around an IMBH—a dark matter spike—can affect the orbital evolution of the system. We consider here such intermediate mass ratio inspirals on eccentric orbits, experiencing dynamical friction of the dark matter spike. We find that by including the relative velocities of the dark matter particles, the dynamical friction tends to circularize the orbit, in contrast to previous inquiries. We derive a general condition for circularization or eccentrification for any given dissipative force. In addition to the dephasing, we suggest using the circularization rate as another probe of the dark matter spike. Observing these effects would be an indicator for the particle nature of dark matter.
Circularization vs. eccentrification in intermediate mass ratio inspirals inside dark matter spikes
(2022)
Inspirals of an Intermediate Mass Black Hole (IMBH) and a solar mass type object will be observable by space based gravitational wave detectors such as The Laser Interferometer Space Antenna (LISA). A dark matter overdensity around an IMBH - a dark matter spike - can affect the orbital evolution of the system. We consider here such Intermediate Mass Ratio Inspirals on eccentric orbits, experiencing dynamical friction of the dark matter spike. We find that by including the phase space distribution of the dark matter, the dynamical friction tends to circularize the orbit, in contrast to previous inquiries. We derive a general condition for circularization or eccentrification for any given dissipative force. In addition to the dephasing, we suggest using the circularization rate as another probe of the dark matter spike. Observing these effects would be an indicator for the particle nature of dark matter.
Circularization vs. eccentrification in intermediate mass ratio inspirals inside dark matter spikes
(2021)
Inspirals of an Intermediate Mass Black Hole (IMBH) and a solar mass type object will be observable by space based gravitational wave detectors such as The Laser Interferometer Space Antenna (LISA). A dark matter overdensity around an IMBH - a dark matter spike - can affect the orbital evolution of the system. We consider here such Intermediate Mass Ratio Inspirals on eccentric orbits, experiencing dynamical friction of the dark matter spike. We find that by including the phase space distribution of the dark matter, the dynamical friction tends to circularize the orbit, in contrast to previous inquiries. We derive a general condition for circularization or eccentrification for any given dissipative force. In addition to the dephasing, we suggest using the circularization rate as another probe of the dark matter spike. Observing these effects would be an indicator for the particle nature of dark matter.
The dipole strength distribution of 130Te was investigated with the method of Nuclear Resonance Fluorescence using continuous-energy bremsstrahlung at the Darmstadt High Intensity Photon Setup and quasi-monoenergetic photons at the High Intensity γ-Ray Source. The average decay properties were determined between 5.50 and 8.15 MeV and compared to simulations within the statistical model.
Dark matter could accumulate around neutron stars in sufficient amounts to affect their global properties. In this work, we study the effect of a specific model for dark matter—a massive and self-interacting vector (spin-1) field—on neutron stars. We describe the combined systems of neutron stars and vector dark matter using Einstein–Proca theory coupled to a nuclear matter term and find scaling relations between the field and metric components in the equations of motion. We construct equilibrium solutions of the combined systems, compute their masses and radii, and also analyze their stability and higher modes. The combined systems admit dark matter (DM) core and cloud solutions. Core solutions compactify the neutron star component and tend to decrease the total mass of the combined system. Cloud solutions have the inverse effect. Electromagnetic observations of certain cloud-like configurations would appear to violate the Buchdahl limit. This could make Buchdahl-limit-violating objects smoking gun signals for dark matter in neutron stars. The self-interaction strength is found to significantly affect both mass and radius. We also compare fermion Proca stars to objects where the dark matter is modeled using a complex scalar field. We find that fermion Proca stars tend to be more massive and geometrically larger than their scalar field counterparts for equal boson masses and self-interaction strengths. Both systems can produce degenerate masses and radii for different amounts of DM and DM particle masses.
Dark matter could accumulate around neutron stars in sufficient amounts to affect their global properties. In this work, we study the effect of a specific model for dark matter -- a massive and self-interacting vector (spin-1) field -- on neutron stars. We describe the combined systems of neutron stars and vector dark matter using Einstein-Proca theory coupled to a nuclear-matter term, and find scaling relations between the field and metric components in the equations of motion. We construct equilibrium solutions of the combined systems, compute their masses and radii and also analyse their stability and higher modes. The combined systems admit dark matter (DM) core and cloud solutions. Core solutions compactify the neutron star component and tend to decrease the total mass of the combined system. Cloud solutions have the inverse effect. Electromagnetic observations of certain cloud-like configurations would appear to violate the Buchdahl limit. This could make Buchdahl-limit violating objects smoking gun signals for dark matter in neutron stars. The self-interaction strength is found to significantly affect both mass and radius. We also compare fermion Proca stars to objects where the dark matter is modelled using a complex scalar field. We find that fermion Proca stars tend to be more massive and geometrically larger than their scalar field counterparts for equal boson masses and self-interaction strengths. Both systems can produce degenerate masses and radii for different amounts of DM and DM particle masses.
Dark matter could accumulate around neutron stars in sufficient amounts to affect their global properties. In this work, we study the effect of a specific model for dark matter -- a massive and self-interacting vector (spin-1) field -- on neutron stars. We describe the combined systems of neutron stars and vector dark matter using Einstein-Proca theory coupled to a nuclear-matter term, and find scaling relations between the field and metric components in the equations of motion. We construct equilibrium solutions of the combined systems, compute their masses and radii and also analyse their stability and higher modes. The combined systems admit dark matter (DM) core and cloud solutions. Core solutions compactify the neutron star component and tend to decrease the total mass of the combined system. Cloud solutions have the inverse effect. Electromagnetic observations of certain cloud-like configurations would appear to violate the Buchdahl limit. This could make Buchdahl-limit violating objects smoking gun signals for dark matter in neutron stars. The self-interaction strength is found to significantly affect both mass and radius. We also compare fermion Proca stars to objects where the dark matter is modelled using a complex scalar field. We find that fermion Proca stars tend to be more massive and geometrically larger than their scalar field counterparts for equal boson masses and self-interaction strengths. Both systems can produce degenerate masses and radii for different amounts of DM and DM particle masses.