Demonstration of K-Kbar, B-Bbar, and D-Dbar Transitions with a Pair of Coupled Pendula

A setup of two coupled and damped pendula is used to demonstrate the main features of transitions beween neutral K, D, B mesons and their respective antiparticles, including CP violation in K Kbar transitions. The transitions are described by two-state Schr\"odinger equations. Since the real parts of their solutions obey the same differential equations as the pendula coordinates, the pendulum motions can be used to represent the meson transitions. Video clips of the motions are attached as supplementary material.Comment: 15 pages, 6 figure

JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions

Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis

Substituted Ge–Sb–Te materials: structure, element distribution and thermoelectric properties

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PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.

Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels

Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19

The systemic immune response to viral infection is shaped by master transcription fac-tors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs)have been suggested as important regulators of transcription factor activity, their contri-butions to the systemic immunopathologies observed during SARS-CoV-2 infectionhave remained unknown. Here, we employed a targeted single-cell RNA sequencingapproach to reveal lncRNAs differentially expressed in blood leukocytes during severeCOVID-19. Our results uncover the lncRNA PIRAT (PU.1-induced regulator of alar-min transcription) as a major PU.1 feedback-regulator in monocytes, governing the pro-duction of the alarmins S100A8/A9, key drivers of COVID-19 pathogenesis. Knockoutand transgene expression, combined with chromatin-occupancy profiling, characterizedPIRATasanucleardecoyRNA,keepingPU.1frombindingtoalarminpromotersandpromoting its binding to pseudogenes in naïve monocytes. NF-κB–dependent PIRATdown-regulation during COVID-19 consequently releases a transcriptional brake, fuelingalarmin production. Alarmin expression is additionally enhanced by the up-regulation ofthe lncRNA LUCAT1, which promotes NF-κB–dependentgeneexpressionattheexpenseof targets of the JAK-STAT pathway. Our results suggest a major role of nuclear noncod-ing RNA networks in systemic antiviral responses to SARS-CoV-2 in humans

C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity

The p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA-binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity: while p53 and the p73 isoform p73γ have basic CTDs and form weak sequence-specific protein–DNA complexes, the major p73 isoforms have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein–DNA complex stability, intranuclear mobility, promoter occupancy in vivo, target gene activation and induction of cell cycle arrest or apoptosis. A basic CTD therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. The different DNA-binding characteristics of the p53 family members could therefore reflect their predominant role in the cellular stress response (p53) or developmental processes (p73)

Determination of the Michel Parameters rho, xi, and delta in tau-Lepton Decays with tau --> rho nu Tags

Using the ARGUS detector at the $e^+ e^-$ storage ring DORIS II, we have measured the Michel parameters $\rho$, $\xi$, and $\xi\delta$ for $\tau^{\pm}\to l^{\pm} \nu\bar\nu$ decays in $\tau$-pair events produced at center of mass energies in the region of the $\Upsilon$ resonances. Using $\tau^\mp \to \rho^\mp \nu$ as spin analyzing tags, we find $\rho_{e}=0.68\pm 0.04 \pm 0.08$, $\xi_{e}= 1.12 \pm 0.20 \pm 0.09$, $\xi\delta_{e}= 0.57 \pm 0.14 \pm 0.07$, $\rho_{\mu}= 0.69 \pm 0.06 \pm 0.08$, $\xi_{\mu}= 1.25 \pm 0.27 \pm 0.14$ and $\xi\delta_{\mu}= 0.72 \pm 0.18 \pm 0.10$. In addition, we report the combined ARGUS results on $\rho$, $\xi$, and $\xi\delta$ using this work und previous measurements.Comment: 10 pages, well formatted postscript can be found at http://pktw06.phy.tu-dresden.de/iktp/pub/desy97-194.p

Searches at HERA for Squarks in R-Parity Violating Supersymmetry

A search for squarks in R-parity violating supersymmetry is performed in e^+p collisions at HERA at a centre of mass energy of 300 GeV, using H1 data corresponding to an integrated luminosity of 37 pb^(-1). The direct production of single squarks of any generation in positron-quark fusion via a Yukawa coupling lambda' is considered, taking into account R-parity violating and conserving decays of the squarks. No significant deviation from the Standard Model expectation is found. The results are interpreted in terms of constraints within the Minimal Supersymmetric Standard Model (MSSM), the constrained MSSM and the minimal Supergravity model, and their sensitivity to the model parameters is studied in detail. For a Yukawa coupling of electromagnetic strength, squark masses below 260 GeV are excluded at 95% confidence level in a large part of the parameter space. For a 100 times smaller coupling strength masses up to 182 GeV are excluded.Comment: 32 pages, 14 figures, 3 table

Prognostic value of increase in transcript levels of Tp73 ΔEx2-3 isoforms in low-grade glioma patients

Glial tumours are a devastating, poorly understood condition carrying a gloomy prognosis for which clinicians sorely lack reliable predictive parameters facilitating a sound treatment strategy. Tp73, a p53 family member, expresses two main classes of isoforms – transactivatory activity (TA)p73 and ΔTAp73 – exhibiting tumour suppressor gene and oncogene properties, respectively. The authors examined their expression status in high- and low-grade adult gliomas. Isoform-specific real-time reverse transcription-polymerase chain reaction was used for the analysis of Tp73 isoform transcript expression in a series of 51 adult patients harbouring glial tumours, in order to compare tumour grades with each other, and with non-tumoural samples obtained from epileptic patients as well. Our data demonstrate increase of TAp73 and ΔTAp73 transcript levels at onset and early stage of the disease. We also show that ΔEx2–3 isoform expression in low-grade tumours anticipates clinical and imaging progression to higher grades, and correlates to the patients' survival. Expression levels of P1 promoter generated Tp73 isoforms – and particularly ΔEx2–3 – indeed allow for prediction of the clinical progression of low-grade gliomas in adults. Our data are the first such molecular biology report regarding low-grade tumours and as such should be of help for sound decision-making