The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies

Predictive significance of the six-minute walk distance for long-term survival in chronic hypercapnic respiratory failure

Background: The 6-min walk distance ( 6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease ( COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure ( CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation ( NIV) comprising COPD ( n = 197), restrictive diseases ( RD; n = 112) and obesity-hypoventilation- syndrome ( OHS; n = 115), the prognostic value of 6-MWD for long- term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD ( median 280 m; quartiles 204/350 m) and RD ( 290 m; 204/362 m) compared to OHS ( 360 m; 275/440 m; p <0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s ( p <0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median {[} p <0.001, hazard ratio ( HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long- term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF. Copyright (C) 2007 S. Karger AG, Basel

Radiative neutron capture cross-section measurement of ge isotopes at n_TOF CERN facility and its importance for stellar nucleosynthesis

This manuscript summarizes the results of radiative neutron capture cross-section measurements on two stable germanium isotopes, 70Ge and 73Ge. Experiments were performed at the n_TOF facility at CERN via the time-of-flight technique, over a wide neutron energy range, for all stable germanium isotopes (70,72,73,74, and 76). Results for 70Ge [Phys. Rev. C 100, 045804 (2019)] and 73Ge [Phys. Lett. B 790, 458 (2019)] are already published. In the field of nuclear structure, such measurements allow to study excited levels close to the neutron binding energy and to obtain information on nuclear properties. In stellar nucleosynthesis research, neutron induced reactions on germanium are of importance for nucleosynthesis in the weak component of the slow neutron capture processes.Peer ReviewedArticle signat per 134 autors/autores: A. Gawlik, C. Lederer-Woods, J. Andrzejewski, J. Perkowski, U. Battino, P. Ferreira, F. Gunsing, S. Heinitz, M. Krtička, C. Massimi, F. Mingrone, R. Reifarth, A. Tattersall, S. Valenta, C. Weiss, O. Aberle, L. Audouin, M. Bacak, J. Balibrea, M. Barbagallo, S. Barros, V. Bécares, F. Bečvář, C. Beinrucker, E. Berthoumieux, J. Billowes, D. Bosnar, M. Brugger, M. Caamaño, F. Calviño, M. Calviani, D. Cano-Ott, R. Cardella, A. Casanovas, D.M. Castelluccio, F. Cerutti, Y.H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M.A. Cortés-Giraldo, L. Cosentino, L.A. Damone, M. Diakaki, M. Dietz, C. Domingo-Pardo, R. Dressler, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Finocchiaro, V. Furman, K. Göbel, A.R. García, T. Glodariu, I.F. Gonçalves, E. González-Romero, A. Goverdovski, E. Griesmayer, C. Guerrero, H. Harada, T. Heftrich, J. Heyse, D.G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, T. Katabuchi, P. Kavrigin, V. Ketlerov, V. Khryachkov, A. Kimura, N. Kivel, I. Knapova, M. Kokkoris, E. Leal-Cidoncha, H. Leeb, J. Lerendegui-Marco, S. Lo Meo, S.J. Lonsdale, R. Losito, D. Macina, T. Martínez, P. Mastinu, M. Mastromarco, F. Matteucci, E.A. Maugeri, E. Mendoza, A. Mengoni, P.M. Milazzo, M. Mirea, S. Montesano, A. Musumarra, R. Nolte, A. Oprea, N. Patronis, A. Pavlik, J.I. Porras, J. Praena, J.M. Quesada, K. Rajeev, T. Rauscher, A. Riego-Perez, P.C. Rout, C. Rubbia, J.A. Ryan, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, S. Schmidt, D. Schumann, P. Sedyshev, A.G. Smith, A. Stamatopoulos, G. Tagliente, J.L. Tain, A. Tarifeño-Saldivia, L. Tassan-Got, A. Tsinganis, G. Vannini, V. Variale, P. Vaz, A. Ventura, V. Vlachoudis, R. Vlastou, A. Wallner, S. Warren, M. Weigand, C. Wolf, P.J. Woods, T. Wright, P. ŽugecObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (author's final draft

74 Ge(n, ¿) cross section below 70 keV measured at n_TOF CERN

The version of record os available online at:https://doi.org/10.1140/epja/s10050-022-00878-5Neutron capture reaction cross sections on 74Ge are of importance to determine 74Ge production during the astrophysical slow neutron capture process. We present new resonancedataon74Ge(n,¿)reactionsbelow70keVneutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experimentPeer ReviewedArticle escrit per 123 autors/autores C. Lederer-Woods, O. Aberle, J. Andrzejewski, L. Audouin, V. Bécares, M. Bacak, J. Balibrea, M. Barbagallo, S. Barros, U. Battino, F. Bečvář, C. Beinrucker, E. Berthoumieux, J. Billowes, D. Bosnar, M. Brugger, M. Caamaño, F. Calviño, M. Calviani, D. Cano-Ott, R. Cardella, A. Casanovas, D. M. Castelluccio, F. Cerutti, Y. H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M. A. Cortés-Giraldo, L. Cosentino, L. A. Damone, M. Diakaki, C. Domingo-Pardo, R. Dressler, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Ferreira, P. Finocchiaro, V. Furman, K. Göbel, A. R. García, A. Gawlik-Ramięga, T. Glodariu, I. F. Gonçalves, E. González-Romero, A. Goverdovski, E. Griesmayer, C. Guerrero, F. Gunsing, H. Harada, T. Heftrich, S. Heinitz, J. Heyse, D. G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, T. Katabuchi, P. Kavrigin, V. Ketlerov, V. Khryachkov, A. Kimura, N. Kivel, M. Kokkoris, M. Krtička, E. Leal-Cidoncha, H. Leeb, J. Lerendegui-Marco, S. Lo Meo, S. J. Lonsdale, R. Losito, D. Macina, J. Marganiec, T. Martínez, C. Massimi, P. Mastinu, M. Mastromarco, F. Matteucci, E. A. Maugeri, E. Mendoza, A. Mengoni, P. M. Milazzo, F. Mingrone, M. Mirea, S. Montesano, A. Musumarra, R. Nolte, A. Oprea, N. Patronis, A. Pavlik, J. Perkowski, I. Porras, J. Praena, J. M. Quesada, K. Rajeev, T. Rauscher, R. Reifarth, A. Riego-Perez, P. C. Rout, C. Rubbia, J. A. Ryan, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, S. Schmidt, D. Schumann, P. Sedyshev, A. G. Smith, A. Stamatopoulos, G. Tagliente, J. L. Tain, A. Tarifeño-Saldivia, L. Tassan-Got, A. Tsinganis, S. Valenta, G. Vannini, V. Variale, P. Vaz, A. Ventura, V. Vlachoudis, R. Vlastou, A. Wallner, S. Warren, M. Weigand, C. Weiss, C. Wolf, P. J. Woods, T. Wright, P. ŽugecPostprint (published version

Heterogeneous Nuclear Ribonucleoprotein K Interacts with Abi-1 at Postsynaptic Sites and Modulates Dendritic Spine Morphology

BACKGROUND: Abelson-interacting protein 1 (Abi-1) plays an important role for dendritic branching and synapse formation in the central nervous system. It is localized at the postsynaptic density (PSD) and rapidly translocates to the nucleus upon synaptic stimulation. At PSDs Abi-1 is in a complex with several other proteins including WASP/WAVE or cortactin thereby regulating the actin cytoskeleton via the Arp 2/3 complex. PRINCIPAL FINDINGS: We identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a 65 kDa ssDNA/RNA-binding-protein that is involved in multiple intracellular signaling cascades, as a binding partner of Abi-1 at postsynaptic sites. The interaction with the Abi-1 SH3 domain is mediated by the hnRNPK-interaction (KI) domain. We further show that during brain development, hnRNPK expression becomes more and more restricted to granule cells of the cerebellum and hippocampal neurons where it localizes in the cell nucleus as well as in the spine/dendritic compartment. The downregulation of hnRNPK in cultured hippocampal neurons by RNAi results in an enlarged dendritic tree and a significant increase in filopodia formation. This is accompanied by a decrease in the number of mature synapses. Both effects therefore mimic the neuronal morphology after downregulation of Abi-1 mRNA in neurons. CONCLUSIONS: Our findings demonstrate a novel interplay between hnRNPK and Abi-1 in the nucleus and at synaptic sites and show obvious similarities regarding both protein knockdown phenotypes. This indicates that hnRNPK and Abi-1 act synergistic in a multiprotein complex that regulates the crucial balance between filopodia formation and synaptic maturation in neurons

Disordered enthalpy–entropy descriptor for high-entropy ceramics discovery

The need for improved functionalities in extreme environments is fuelling interest in high-entropy ceramics1,2,3. Except for the computational discovery of high-entropy carbides, performed with the entropy-forming-ability descriptor4, most innovation has been slowly driven by experimental means1,2,3. Hence, advancement in the field needs more theoretical contributions. Here we introduce disordered enthalpy–entropy descriptor (DEED), a descriptor that captures the balance between entropy gains and enthalpy costs, allowing the correct classification of functional synthesizability of multicomponent ceramics, regardless of chemistry and structure. To make our calculations possible, we have developed a convolutional algorithm that drastically reduces computational resources. Moreover, DEED guides the experimental discovery of new single-phase high-entropy carbonitrides and borides. This work, integrated into the AFLOW computational ecosystem, provides an array of potential new candidates, ripe for experimental discoveries

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of “modifiable risk factors”, measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details

Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIδC can be reversed by inhibition of late Na+ current

Transgenic (TG) Ca2+/calmodulin-dependent protein kinase II (CaMKII) δC mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca2+ handling proteins as well as sarcolemmal Na+ channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na+ current (late INa) in early HF (8-week-old TG mice). Echocardiography revealed severe diastolic dysfunction in addition to decreased systolic ejection fraction. Premature arrhythmogenic contractions (PACs) in isolated isometrically twitching papillary muscles only occurred in TG preparations (5 vs. 0, P < 0.05) which could be completely terminated when treated with the late INa inhibitor ranolazine (Ran, 5 μmol/L). Force–frequency relationships revealed significantly reduced twitch force amplitudes in TG papillary muscles. Most importantly, diastolic tension increased with raising frequencies to a greater extent in TG papillary muscles compared to WT specimen (at 10 Hz: 3.7 ± 0.4 vs. 2.5 ± 0.3 mN/mm2; P < 0.05). Addition of Ran improved diastolic dysfunction to 2.1 ± 0.2 mN/mm2 (at 10 Hz; P < 0.05) without negative inotropic effects. Mechanistically, the late INa was markedly elevated in myocytes isolated from TG mice and could be completely reversed by Ran. In conclusion, our results show for the first time that TG CaMKIIδC overexpression induces diastolic dysfunction and arrhythmogenic triggers possibly via an enhanced late INa. Inhibition of elevated late INa had beneficial effects on arrhythmias as well as diastolic function in papillary muscles from CaMKIIδC TG mice. Thus, late INa inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased

Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis

Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephriti