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Kidney injury is a common complication of severe disease. Here, we report that injuries of the zebrafish embryonal kidney are rapidly repaired by a migratory response in 2-, but not in 1-day-old embryos. Gene expression profiles between these two developmental stages identify cxcl12a and myca as candidates involved in the repair process. Zebrafish embryos with cxcl12a, cxcr4b, or myca deficiency display repair abnormalities, confirming their role in response to injury. In mice with a kidney-specific knockout, Cxcl12 and Myc gene deletions suppress mitochondrial metabolism and glycolysis, and delay the recovery after ischemia/reperfusion injury. Probing these observations in zebrafish reveal that inhibition of glycolysis slows fast migrating cells and delays the repair after injury, but does not affect the slow cell movements during kidney development. Our findings demonstrate that Cxcl12 and Myc facilitate glycolysis to promote fast migratory responses during development and repair, and potentially also during tumor invasion and metastasis.
Immunosuppression is a typical hallmark of cancer and frequently includes perturbations of the NKG2D tumor recognition system as well as impaired signaling by other activating NK cell receptors. Several in vitro studies suggested that sustained engagement of the NKG2D receptor, as it is occurring in the tumor microenvironment, not only impairs expression and function of NKG2D but also impacts signaling by other activating NK receptors. Here, we made use of a transgenic mouse model of ubiquitous NKG2D ligand expression (H2-Kb-MICA mice) to investigate consequences of chronic NKG2D engagement in vivo for functional responsiveness by other activating NK receptors such as NKp46 and Ly49D. Unexpectedly, we found no evidence for an impairment of NKp46 expression and function in H2-Kb-MICA mice, as anticipated from previous in vitro experiments. However, we observed a marked downregulation and dysfunction of the activating receptor Ly49D in activated NK cells from H2-Kb-MICA mice. Ly49D shares the adaptor proteins DAP10 and DAP12 with NKG2D possibly explaining the collateral impairment of Ly49D function in situations of chronic NKG2D engagement. Altogether, our results demonstrate that persistent engagement of NKG2D in vivo, as often observed in tumors, can selectively impair functions of unrelated NK receptors and thereby compromise NK responsiveness to third-party antigens.
The industry‐scale production of methylchloromonosilanes in the Müller–Rochow Direct Process is accompanied by the formation of a residue, the direct process residue (DPR), comprised of disilanes MenSi2Cl6‐n (n=1–6). Great research efforts have been devoted to the recycling of these disilanes into monosilanes to allow reintroduction into the siloxane production chain. In this work, disilane cleavage by using alkali and alkaline earth metal salts is reported. The reaction with metal hydrides, in particular lithium hydride (LiH), leads to efficient reduction of chlorine containing disilanes but also induces disproportionation into mono‐ and oligosilanes. Alkali and alkaline earth chlorides, formed in the course of the reduction, specifically induce disproportionation of highly chlorinated disilanes, whereas highly methylated disilanes (n>3) remain unreacted. Nearly quantitative DPR conversion into monosilanes was achieved by using concentrated HCl/ether solutions in the presence of lithium chloride.
Background: School attendance during the COVID-19 pandemic is intensely debated.
Aim: In November 2020, we assessed SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: We collected oro-nasopharyngeal swabs and blood samples, examining SARS-CoV-2 infection and IgG antibodies by RT-PCR and ELISA. Household members self-swabbed. We assessed individual and institutional prevention measures. Classes with SARS-CoV-2 infection and connected households were retested after 1 week.
Results: We examined 1,119 participants, including 177 primary and 175 secondary school students, 142 staff and 625 household members. SARS-CoV-2 infection occurred in eight classes, affecting each 1–2 individuals. Infection prevalence was 2.7% (95% confidence interval (CI): 1.2–5.0; 9/338), 1.4% (95% CI: 0.2–5.1; 2/140), and 2.3% (95% CI: 1.3–3.8; 14/611) among students, staff and household members. Six of nine infected students were asymptomatic at testing. We detected IgG antibodies in 2.0% (95%CI: 0.8–4.1; 7/347), 1.4% (95% CI: 0.2–5.0; 2/141) and 1.4% (95% CI: 0.6–2.7; 8/576). Prevalence increased with inconsistent facemask-use in school, walking to school, and case-contacts outside school. For three of nine households with infection(s), origin in school seemed possible. After 1 week, no school-related secondary infections appeared in affected classes; the attack rate in connected households was 1.1%.
Conclusion: School attendance under rigorously implemented preventive measures seems reasonable. Balancing risks and benefits of school closures need to consider possible spill-over infection into households. Deeper insight is required into the infection risks due to being a schoolchild vs attending school.
Background: School attendance during the SARS-CoV-2 pandemic is intensely debated. Modelling studies suggest that school closures contribute to community transmission reduction. However, data among school-attending students and staff are scarce. In November 2020, we examined SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: Students and school staff were examined, oro-nasopharyngeal swabs and blood samples collected, and SARS-CoV-2 infection and IgG antibodies detected by RT-PCR and ELISA. Household members performed self-swabs. Individual and institutional infection prevention and control measures were assessed. Classes with SARS-CoV-2 infection and connected household members were re-tested after one week.
Findings: 1119 participants were examined, including 177 primary and 175 secondary school students, 142 staff, and 625 household members. Participants reported mainly cold symptoms (19·4%). SARS-CoV-2 infection occurred in eight of 24 classes affecting each 1-2 individuals. Infection prevalence was 2·7% (95%CI; 1·2-5·0%; 9/338), 1·4% (0·2-5·1%; 2/140), and 2·3% (1·3-3·8%; 14/611) among students, staff and household members, respectively, including quarantined persons. Six of nine infected students were asymptomatic. Prevalence increased with inconsistent facemask use in school, way to school on foot, and case-contacts outside school. IgG antibodies were detected in 2·0% (0·8-4·1%; 7/347), 1·4% (0·2-5·0%; 2/141) and 1·4% (0·6-2·7%; 8/576), respectively. For three of nine households with infection(s) detected at cross-sectional assessment, origin in school seemed possible. After one week, no school-related, secondary infections appeared in affected classes; the attack rate in connected households was 1·1%.
Interpretation: These data suggest that school attendance under preventive measures is feasible, provided their rigorous implementation. In balancing threats and benefits of open versus closed schools during the pandemic, parents and society need to consider possible spill-overs into their households. Deeper insight is needed into the infection risks due to being a schoolchild as compared to attending school.
In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets
(2021)
High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients’ leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.
This study investigated the effects of a daily plyometric hopping intervention on running economy (RE) in amateur runners. In a randomized, controlled trial, thirty-four amateur runners (29 ± 7 years, 27 males) were allocated to a control or a hopping exercise group. During the six-week study, the exercise group performed 5 min of double-legged hopping exercise daily. To progressively increase loading, the number of hopping bouts (10 s each) was steadily increased while break duration between sets was decreased. Pre- and post-intervention, RE, peak oxygen uptake (VO2peak), and respiratory exchange ratio (RER) were measured during 4-min stages at three running speeds (10, 12, and 14 km/h). ANCOVAs with baseline values and potential cofounders as cofactors were performed to identify differences between groups. ANCOVA revealed an effect of hopping on RE at 12 km/h (df = 1; F = 4.35; p < 0.05; η2 = 0.072) and 14 km/h (df = 1; F = 6.72; p < 0.05; η2 = 0.098), but not at 10 km/h (p > 0.05). Exercise did not affect VO2peak (p > 0.05), but increased RER at 12 km/h (df = 1; F = 4.26; p < 0.05; η2 = 0.059) and 14 km/h (df = 1; F = 36.73; p < 0.001; η2 = 0.520). No difference in RER was observed at 10 km/h (p > 0.05). Daily hopping exercise is effective in improving RE at high running speeds in amateurs and thus can be considered a feasible complementary training program.
Clinical trial registration German Register of Clinical Trials (DRKS00017373).
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Conclusion: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients
Background: Protection against airborne infection is currently, due to the COVID-19-associated restrictions, ubiquitously applied during public transport use, work and leisure time. Increased carbon dioxide re-inhalation and breathing resistance may result thereof and, in turn, may negatively impact metabolism and performance.
Objectives: To deduce the impact of the surgical mask and filtering face piece type 2 (FFP2) or N95 respirator application on gas exchange (pulse-derived oxygen saturation (SpO2), carbon dioxide partial pressure (PCO2), carbon dioxide exhalation (VCO2) and oxygen uptake (VO2)), pulmonary function (respiratory rate and ventilation) and physical performance (heart rate HR, peak power output Wpeak).
Methods: Systematic review with meta-analysis. Literature available in Medline/Pubmed, the Cochrane Library and the Web of Knowledge with the last search on the 6th of May 2021. Eligibility criteria: Randomised controlled parallel group or crossover trials (RCT), full-text availability, comparison of the acute effects of ≥ 1 intervention (surgical mask or FFP2/N95 application) to a control/comparator condition (i.e. no mask wearing). Participants were required to be healthy humans and > 16 years of age without conditions or illnesses influencing pulmonary function or metabolism. Risk of bias was rated using the crossover extension of the Cochrane risk of bias assessment tool II. Standardised mean differences (SMD, Hedges' g) with 95% confidence intervals (CI) were calculated, overall and for subgroups based on mask and exercise type, as pooled effect size estimators in our random-effects meta-analysis.
Results: Of the 1499 records retrieved, 14 RCTs (all crossover trials, high risk of bias) with 25 independent intervention arms (effect sizes per outcome) on 246 participants were included. Masks led to a decrease in SpO2 during vigorous intensity exercise (6 effect sizes; SMD = − 0.40 [95% CI: − 0.70, − 0.09], mostly attributed to FFP2/N95) and to a SpO2-increase during rest (5 effect sizes; SMD = 0.34 [95% CI: 0.04, 0.64]); no general effect of mask wearing on SpO2 occurred (21 effect sizes, SMD = 0.34 [95% CI: 0.04, 0.64]). Wearing a mask led to a general oxygen uptake decrease (5 effect sizes, SMD = − 0.44 [95% CI: − 0.75, − 0.14]), to slower respiratory rates (15 effect sizes, SMD = − 0.25 [95% CI: − 0.44, − 0.06]) and to a decreased ventilation (11 effect sizes, SMD = − 0.43 [95% CI: − 0.74, − 0.12]). Heart rate (25 effect sizes; SMD = 0.05 [95% CI: − 0.09, 0.19]), Wpeak (9 effect sizes; SMD = − 0.12 [95% CI: − 0.39, 0.15]), PCO2 (11 effect sizes; SMD = 0.07 [95% CI: − 0.14, 0.29]) and VCO2 (4 effect sizes, SMD = − 0.30 [95% CI: − 0.71, 0.10]) were not different to the control, either in total or dependent on mask type or physical activity status.
Conclusion: The number of crossover-RCT studies was low and the designs displayed a high risk of bias. The within-mask- and -intensity-homogeneous effects on gas exchange kinetics indicated larger detrimental effects during exhausting physical activities. Pulse-derived oxygen saturation was increased during rest when a mask was applied, whereas wearing a mask during exhausting exercise led to decreased oxygen saturation. Breathing frequency and ventilation adaptations were not related to exercise intensity. FFP2/N95 and, to a lesser extent, surgical mask application negatively impacted the capacity for gas exchange and pulmonary function but not the peak physical performance.
Registration: Prospero registration number: CRD42021244634
Mask induced airway resistance and carbon dioxide rebreathing is discussed to impact gas exchange and to induce discomfort and impairments in cognitive performance. N = 23 healthy humans (13 females, 10 males; 23.5 ± 2.1 years) participated in this randomized crossover trial (3 arms, 48-h washout periods). During interventions participants wore either a surgical face mask (SM), a filtering face piece (FFP2) or no mask (NM). Interventions included a 20-min siting period and 20 min steady state cycling on an ergometer at 77% of the maximal heart rate (HR). Hemodynamic data (HR, blood pressure), metabolic outcomes (pulse derived oxygen saturation, capillary carbon dioxide (pCO2), and oxygen partial pressure (pO2), lactate, pH, base excess), subjective response (ability to concentrate, arousal, perceived exertion) and cognitive performance (Stroop Test) were assessed. Compared to NM, both masks increased pCO2 (NM 31.9 ± 3.3 mmHg, SM = 35.2 ± 4.0 mmHg, FFP2 = 34.5 ± 3.8 mmHg, F = 12.670, p < 0.001) and decreased pH (NM = 7.42 ± 0.03, SM = 7.39 ± 0.03, FFP2 = 7.39 ± 0.04, F = 11.4, p < 0.001) during exercise. The FFP2 increased blood pressure during exercise (NM = 158 ± 15 mmHg, SM = 159 ± 16 mmHg, FFP2 = 162 ± 17 mmHg, F = 3.21, p = 0.050), the SM increased HR during sitting (NM = 70 ± 8 bpm, SM = 74 ± 8 bpm, FFP2 = 73 ± 8 bpm, F = 4.70, p = 0.014). No mask showed any comparative effect on other hemodynamic, metabolic, subjective, or cognitive outcomes. Mask wearing leads to slightly increased cardiovascular stress and elevated carbon dioxide levels during exercise but did not affect cognitive performance or wellbeing.
Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.
A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets
(2018)
NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.
Background & aims: Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.
Methods: This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.
Results: A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002).
Conclusions: This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines.
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).
We measure the inclusive semielectronic decay branching fraction of the D+s meson. A double-tag technique is applied to e+e− annihilation data collected by the BESIII experiment at the BEPCII collider, operating in the center-of-mass energy range 4.178–4.230 GeV. We select positrons fromD+s→Xe+νe with momenta greater than 200 MeV/c and determine the laboratory momentum spectrum, accounting for the effects of detector efficiency and resolution. The total positron yield and semielectronic branching fraction are determined by extrapolating this spectrum below the momentum cutoff. We measure the D+s semielectronic branching fraction to be(6.30±0.13(stat.)±0.09(syst.)±0.04(ext.))%, showing no evidence for unobserved exclusive semielectronic modes. We combine this result with external data taken from literature to determine the ratio of the D+s and D0 semielectronic widths, Γ(D+s→Xe+νe)Γ(D0→Xe+νe)=0.790±0.016(stat.)±0.011(syst.)±0.016(ext.). Our results are consistent with and more precise than previous measurements.
Accurate spectroscopy of highly-charged high-Z ions in a storage ring is demonstrated to be feasible by the use of specially adapted crystal optics. The method has been applied for the measurement of the 1s Lamb shift in hydrogen-like gold (Au+78) in a storage ring through spectroscopy of the Lyman x-rays. This measurement represents the first result obtained for a high-Z element using high-resolution wavelength-dispersive spectroscopy in the hard x-ray regime, paving the way for sensitivity to higher- order QED effects.
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
(2023)
Excitable cells can be stimulated or inhibited by optogenetics. Since optogenetic actuation regimes are often static, neurons and circuits can quickly adapt, allowing perturbation, but not true control. Hence, we established an optogenetic voltage-clamp (OVC). The voltage-indicator QuasAr2 provides information for fast, closed-loop optical feedback to the bidirectional optogenetic actuator BiPOLES. Voltage-dependent fluorescence is held within tight margins, thus clamping the cell to distinct potentials. We established the OVC in muscles and neurons of Caenorhabditis elegans, and transferred it to rat hippocampal neurons in slice culture. Fluorescence signals were calibrated to electrically measured potentials, and wavelengths to currents, enabling to determine optical I/V-relationships. The OVC reports on homeostatically altered cellular physiology in mutants and on Ca2+-channel properties, and can dynamically clamp spiking in C. elegans. Combining non-invasive imaging with control capabilities of electrophysiology, the OVC facilitates high-throughput, contact-less electrophysiology in individual cells and paves the way for true optogenetic control in behaving animals.