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CD4 expression controls epidermal stem cell balance
No full textAbstract The balance of stem cell populations is essential for the maintenance, renewal, and repair of the mammalian epidermis. Here, we report that CD4, which is a typical marker of helper T cells, monocytes, macrophages, and dendritic cells, is also expressed on murine K5 + keratinocytes. Lineage tracing of CD4 + cells reveals that their epidermal progeny has self-renewal abilities and clonogenic potential. The progeny of CD4 + epidermal cells contributes to epidermal renewal and progressively colonizes the interfollicular epidermis and hair follicles with age, thereby developing to all epidermal lineages. Wound healing studies furthermore show that the progeny of CD4 + epidermal cells accumulates at wound sites. Finally, using CD4 knockout mice we demonstrate that CD4 expression is essential for maintaining fast-cycling epidermal stem cells during homeostasis and that CD4 loss mitigates the age-related decline in wound repair capacity. Collectively, our data support the conclusion that CD4 expression is required for long-term maintenance of the epidermal stem cell balance.Open-Access-Publikationsfonds 202
Resonance-enhanced multiphoton ionization detection of vibrationally excited O2
No full textWe report a rotationally resolved spectroscopic detection scheme for vibrationally excited molecular oxygen with high sensitivity. Two-color (2 + 1′) resonance-enhanced multiphoton ionization (REMPI) spectra of O2 hot bands were recorded for the first time via the 3dπ(v′=0)←X3Σg− (v″ = 1) Rydberg transitions. Spectroscopic constants and relative Franck–Condon factors were extracted and compared to simulations. This new access to quantum-state-resolved diagnostics of vibrationally excited O2 promises to shed light on the physical and chemical dynamics of many processes.HORIZON EUROPE European Research Council 10.13039/100019180Israel Science Foundation 10.13039/501100003977Kreitman School of Advanced Graduate Studies, Ben-Gurion University of the Negev 10.13039/501100014385Open University of Israel 10.13039/100017248Deutsche Forschungsgemeinschaft 10.13039/50110000165
CORONATINE INSENSITIVE 1-mediated repression of immunity-related genes in Arabidopsis roots is overcome upon infection with Verticillium longisporum
No full textAbstract Verticillium longisporum is a soil-borne fungal pathogen causing vascular disease predominantly in Brassicaceae. We have reported previously that the receptor of the plant defense hormone jasmonoyl-isoleucine (JA-Ile), CORONATINE INSENSITIVE 1 (COI1), is required in roots for efficient proliferation of the fungus in the shoot implicating a mobile root-borne signal that influences the outcome of the disease in shoots. This susceptibility-promoting COI1 function is independent from JA-Ile. To explore the underlying mechanism we compared the root transcriptome of coi1 with the transcriptomes of the susceptible JA-Ile-deficient allene oxide synthase (aos) mutant and susceptible wild-type (WT) plants. The biggest difference between the transcriptomes of coi1 versus WT and aos was due to 316 immunity-related genes that were constitutively higher expressed in coi1 as compared to the susceptible genotypes. Interfering with the expression of a subgroup of these genes partially suppressed the coi1-mediated tolerance phenotype. We therefore hypothesize that secreted defense compounds encoded by genes constitutively expressed in coi1 are transported to the shoot with the transpiration stream where they accumulate to interfere with fungal growth. We furthermore report that 149 of the 316 COI1-repressed genes are induced in WT and aos upon infection reaching similar levels as in mock-treated coi1. These were not further induced in coi1 upon infection. Thus, the repressive effect of COI1 is either lifted or overridden upon infection with V. longisporum
Electric charge and salting in/out effects on glucagon's dipole moments and polarizabilities using the GruPol database
No full textThis work demonstrates the use of the GruPol database to predict the functional group dipole moments and polarizabilities of glucagon in the presence of NaCl, simulating an electric charge distribution on the protein's backbone. A new feature of the database allows for the inclusion of ions on the protein backbone, effectively simulating a protein salt and predicting the impact on electrical properties. Glucagon was selected as a proof-of-concept molecule due to its relatively small chain, which enabled benchmarking against quantum mechanical calculations. Firstly, we simulated 70 different ionic configurations, varying the number of Na + and Cl − ions from zero to four NaCl moieties. Additionally, we investigated the effects of solvation under two distinct conditions: one involving just the peptide and water, and the other also including NaCl at a concentration of approximately 4.2 mol L −1 . Regarding the ab initio results, GruPol showed good accuracy, with an angular direction error of around 10° and a 15% difference in the magnitude of the dipole moments. However, the error in polarizability values was higher, most likely due to the lack of an augmented basis set in the ab initio quantum calculations (M06-HF/cc-pVDZ). The database entries were generated using the same functional along with the aug-cc-pVDZ basis set. In solution, a high ionic concentration lowered the overall dipole moment, while the main components of polarizability increased.Infrastruktura PL-Grid https://doi.org/10.13039/501100011089Fundação de Amparo à Pesquisa do Estado de Minas Gerais https://doi.org/10.13039/501100004901Conselho Nacional de Desenvolvimento Científico e Tecnológico https://doi.org/10.13039/50110000359
MYSTERY-HF - Myeloperoxidase Inhibition in Patients With Heart Failure and Reduced Ejection Fraction – a Phase II Randomized Controlled Trial
No full textResults of a German national survey to assess early mobilization versus bed rest in the postoperative management of incidental durotomy during lumbar surgery and the need for a randomized clinical trial
No full textOBJECTIVE Incidental durotomy during degenerative lumbar spine surgeries poses a complex medical challenge. Despite its relatively common occurrence, consensus on its management remains elusive due to the absence of robust, high-level evidence, resulting in significant variations in practice across medical institutions. The aim of this survey was to assess the current practices in Germany regarding early mobilization versus bed rest in the postoperative management of incidental durotomy during lumbar surgery to estimate the need for a randomized clinical trial. METHODS A digital survey titled "Postoperative management of incidental durotomy in lumbar spine surgery" was conducted among 119 neurosurgical departments in Germany. Key questions included the use of bed rest postsurgery, timing of mobilization, and whether the practice depended on the complexity of the surgery or the quality of the dural tear repair. The survey also explored the role of lumbar drains in management and respondents’ potential participation in a multicenter study on the benefits of bed rest. RESULTS Invitations were sent in November 2023, and responses were collected during November and December 2023. A total of 89 (75%) departments completed the survey. Among them, 75% reported using bed rest in the postoperative management of incidental durotomy. For 57%, this practice depends on the complexity of the surgical procedure or the quality of the surgical repair of the dural tear, while 18% apply it independently. Twenty-nine of the 89 departments (33%) answered that mobilization is allowed 24 hours after surgery, 13 departments (15%) allow mobilization after 48 hours, and 19 departments (21%) allow it after 72 hours. Additionally, 34% reported using a lumbar drain in cases of persistent postoperative CSF leakage, 36% use it for secondary surgical revision, and 30% do not use it in either case. Furthermore, 55 departments (62%) expressed potential interest in participating in a multicenter randomized trial addressing the postoperative management of incidental durotomy. CONCLUSIONS The postoperative management of incidental durotomy during lumbar surgery exhibits significant variation across neurosurgical departments in Germany. Postoperative bed rest remains a common practice. To evaluate the true benefits of bed rest, a randomized multicenter study is recommended. A summary proposal for such a study is presented to address this need
Fatigue in living kidney donors compared to a German general population sample: an exploratory study
No full textBackground Clinical studies have not conclusively clarified whether fatigue scores in living kidney donors after donation are fundamentally different from general population samples. Moreover, the association between sociodemographic and donor specific factors and fatigue in donors is not well understood. Patients and methods Fatigue scores of 358 living kidney donors on average 7.67 years post-donation were compared with 1896 subjects from the German general population in five strata of age and sex. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI-20). Relationships between the five MFI-20 subscales and the sociodemographic variables sex, age, education, and in the donor sample also years since donation were calculated. Additionally, the association between donor specific variables and fatigue levels were analyzed. Results Overall, donors had lower fatigue scores than the population sample. Particularly the age group 65-74 and above reported significantly lower fatigue scores. A significant exception was found in women aged 45-54 years, where donors showed significant higher general fatigue scores than the corresponding subgroup of the general population sample. Multiple regression analyses in the general population sample revealed associations between female sex and higher age with higher values in most MFI-20 subscales, whereas subjects with higher education showed mostly lower fatigue scores. In the donor group, these associations were of little importance. Also, years since donation, partnership, and recipient group were not strongly related to fatigue. However, higher fatigue in donors was associated with more donation regret, a more negative relationship with the recipient, a more negatively perceived recipient health, less perceived family support, and more financial burden. Conclusion Fatigue is less prevalent particularly in older donors and predictors of fatigue presented in the general population sample seem to have little importance in the donors. However, middle-aged female donors might be more prone to develop fatigue. This group may require more intense exploration before and after donation to detect and treat the underlying factors timely
