Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5′ exonuclease-mediated nucleic acid degradation

The phospholipase D (PLD) family is comprised of enzymes bearing phospholipase activity towards lipids or endo- and exonuclease activity towards nucleic acids. PLD3 is synthesized as a type II transmembrane protein and proteolytically cleaved in lysosomes, yielding a soluble active form. The deficiency of PLD3 leads to the slowed degradation of nucleic acids in lysosomes and chronic activation of nucleic acid-specific intracellular toll-like receptors. While the mechanism of PLD phospholipase activity has been extensively characterized, not much is known about how PLDs bind and hydrolyze nucleic acids. Here, we determined the high-resolution crystal structure of the luminal N-glycosylated domain of human PLD3 in its apo- and single-stranded DNA-bound forms. PLD3 has a typical phospholipase fold and forms homodimers with two independent catalytic centers via a newly identified dimerization interface. The structure of PLD3 in complex with an ssDNA-derived thymidine product in the catalytic center provides insights into the substrate binding mode of nucleic acids in the PLD family. Our structural data suggest a mechanism for substrate binding and nuclease activity in the PLD family and provide the structural basis to design immunomodulatory drugs targeting PLD3

Vivostat Platelet-Rich Fibrin® for Complicated or Chronic Wounds-A Pilot Study

Vivostat Platelet-Rich Fibrin® (PRF) is an autologous platelet concentrate used for the local treatment of chronic or complicated wounds. Still, its application for this indication is not evidence-based. Therefore, we performed this monocentric retrospective pilot study investigating the clinical outcome of a local treatment of chronic or complicated wounds in 35 patients (23 male, 12 female, mean age 68.7 years) treated with Vivostat PRF®. This study population is the largest among published studies analyzing the clinical efficacy of Vivostat PRF® on chronic wounds so far. Using the perpendicular method we divided the wounds into three sizes (30 cm2). The clinical efficacy of the Vivostat PRF treatment was the primary endpoint and was divided into three groups of increasing degrees of wound improvement: (1) no improvement of the wound (wound area was not reduced > 10% under Vivostat PRF® treatment), (2) improvement of the wound (reduced area > 10% under Vivostat PRF® treatment) and (3) complete epithelialization (wounds that were completely re-epithelialized after Vivostat PRF® treatment). We included patients' diagnosis and concomitant diseases (peripheral arterial occlusive disease (PAOD)), chronic venous insufficiency (CVI)), diabetic foot syndrome (DFS)) in our data analysis in order to investigate their potential impact on the wound healing capacity of Vivostat PRF®. Our results show that in the entire study population, 13 out of 35 (37.1%) patients experienced wound improvement and 14 out of 35 (40%) patients showed complete epithelialization of their wound under Vivostat PRF® treatment. In summary, 77.1% of the treated patients benefited from the Vivostat PRF® therapy

A passion for respect: On understanding the role of human needs and morality

In the present paper, we stress the importance of the concept respect in a wide variety of social settings and provide a working definition of this concept by emphasizing how respect relates to the act of communicating full recognition to other people on the dimensions of belongingness and morality. Subsequently, in two separate parts, we discuss why respect is so desired and valued. The first part looks at respect as a means to fulfil important human social concerns (“respect as a means to an end”). The second part looks at the potential moral underpinnings of respect and thus interprets “respect as an end in itself.” Finally, it is suggested that both reasons to value respect explain respect effects as a function of the working selfconcept that is salient (i.e., pragmatic versus idealistic self)

A passion for respect: On understanding the role of human needs and morality

In the present paper, we stress the importance of the concept respect in a wide variety of social settings and provide a working definition of this concept by emphasizing how respect relates to the act of communicating full recognition to other people on the dimensions of belongingness and morality. Subsequently, in two separate parts, we discuss why respect is so desired and valued. The first part looks at respect as a means to fulfil important human social concerns (“respect as a means to an end”). The second part looks at the potential moral underpinnings of respect and thus interprets “respect as an end in itself.” Finally, it is suggested that both reasons to value respect explain respect effects as a function of the working selfconcept that is salient (i.e., pragmatic versus idealistic self)

Comparisons of Blood Parameters, Red Blood Cell Deformability and Circulating Nitric Oxide Between Males and Females Considering Hormonal Contraception: A Longitudinal Gender Study

Red blood cell (RBC) deformability is an important determinant of the microcirculation. It is influenced by various hematological parameters but also by nitric oxide (NO) which is produced in RBC from L-arginine by RBC-NO synthase. Longitudinal studies on blood profile, deformability at rest and NO levels but also differences between males and females (±hormonal contraception; HC) are less known so far. The study thus aimed to investigate RBC deformability, RBC NO species (nitrite, RxNO), RBC L-arginine concentration and basal blood parameters in males and females (±HC) as a function of time. RBC deformability was measured at rest once per week and the remaining parameters were measured once per month, respectively. A second experiment aimed to daily measure RBC deformability and 17β-estradiol in Female ± HC during a whole menstruation cycle to investigate a possible relation of the two parameters. Measured parameters showed low week-to-week variation and remained constant during study period. However, RBC deformability increased in Female + HC during study period possibly because of increasing training volume of the participants. Overall, results indicate gender differences in hematological parameters with higher RBC parameters (RBC count, hematocrit, hemoglobin concentration) in males compared to females. Differences were also observed between the female groups with Females - HC showing lower number of RBC but higher MCV and hematocrit compared to Females + HC. RBC deformability was highest in Females - HC which might be related to permanent higher estradiol levels and/or higher RBC NO levels because RBC nitrite and RBC RxNO concentrations were also highest in Females-HC. Results of the second experiment also suggest higher RBC deformability in Female - HC because of higher estradiol concentrations. L-arginine levels known to be related to RBC NO production were comparable in all groups. In conclusion, hematological, hemorheological and NO related parameters show gender differences. In particular, RBC deformability is affected by training volume and RBC estradiol concentrations. The results add new information on the complex regulation of RBC function which might help to better understand the role of RBC in the microcirculation

Using self-definition to predict the influence of procedural justice on organizational, interpersonal, and job/task-oriented citizenship behaviors

An integrative self-definition model is proposed to improve our understanding of how procedural justice affects different outcome modalities in organizational behavior. Specifically, it is examined whether the strength of different levels of self-definition (collective, relational, and individual) each uniquely interact with procedural justice to predict organizational, interpersonal, and job/task-oriented citizenship behaviors, respectively. Results from experimental and (both single and multisource) field data consistently revealed stronger procedural justice effects (1) on organizational-oriented citizenship behavior among those who define themselves strongly in terms of organizational characteristics, (2) on interpersonal-oriented citizenship behavior among those who define themselves strongly in terms of their interpersonal relationships, and (3) on job/task-oriented citizenship behavior among those who define themselves weakly in terms of their distinctiveness or uniqueness. We discuss the relevance of these results with respect to how employees can be motivated most effectively in organizational settings

Human monocytes subjected to ischaemia/reperfusion inhibit angiogenesis and wound healing in vitro

Objectives The sequence of initial tissue ischaemia and consecutive blood flow restoration leads to ischaemia/reperfusion (I/R) injury, which is typically characterized by a specific inflammatory response. Migrating monocytes seem to mediate the immune response in ischaemic tissues and influence detrimental as well as regenerative effects during I/R injury. Materials and methods To clarify the role of classical monocytes in I/R injury, isolated human monocytes were subjected to I/R in vitro (3 hours ischaemia followed by 24 hours of reperfusion). Cellular resilience, monocyte differentiation, cytokine secretion, as well as influence on endothelial tube formation, migration and cell recovery were investigated. Results We show that I/R supported an enhanced resilience of monocytes and induced intracellular phosphorylation of the prosurvival molecules Erk1/2 and Akt. FACS analysis showed no major alteration in monocyte subtype differentiation and surface marker expression under I/R. Further, our experiments revealed that I/R changes the cytokine secretion pattern, release of angiogenesis associated proteins and MMP-9 activity in supernatants of monocytes exposed to I/R. Supernatants from monocytes subjected to I/R attenuated endothelial tube formation as indicator for angiogenesis as well as endothelial cell migration and recovery. Conclusion In summary, monocytes showed no significant change in cellular integrity and monocyte subtype after I/R. Functionally, monocytes might have a rather detrimental influence during the initial phase of I/R, suppressing endothelial cell migration and neoangiogenesis

Towards a global understanding of vegetation-climate dynamics at multiple timescales

Funding Information: Acknowledgements. This paper has been realized within the Earth System Data Lab project funded by the European Space Agency. The authors acknowledge Lina Fürst for initiation of the preliminary study laying the foundation for this project. The authors acknowledge support from Ulrich Weber for data management and preprocessing. Lina M. Estupinan-Suarez acknowledges the support of the DAAD and its Graduate School Scholarship Programme (57395813). Nora Linscheid acknowledges the support of the TUM Graduate School. Lina M. Estupinan-Suarez and Nora Linscheid acknowledge the continuous support of the International Max Planck Research School for Global Biogeochemical Cycles. Felix Cre-mer acknowledges the support of the German Research Foundation project HyperSense (grant no. TH 1435/4-1). Publisher Copyright: © Author(s) 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Climate variables carry signatures of variability at multiple timescales. How these modes of variability are reflected in the state of the terrestrial biosphere is still not quantified or discussed at the global scale. Here, we set out to gain a global understanding of the relevance of different modes of variability in vegetation greenness and its covariability with climate. We used > 30 years of remote sensing records of the normalized difference vegetation index (NDVI) to characterize biosphere variability across timescales from submonthly oscillations to decadal trends using discrete Fourier decomposition. Climate data of air temperature (Tair) and precipitation (Prec) were used to characterize atmosphere-biosphere covariability at each timescale. Our results show that short-term (intra-annual) and longerterm (interannual and longer) modes of variability make regionally highly important contributions to NDVI variability: short-term oscillations focus in the tropics where they shape 27% of NDVI variability. Longer-term oscillations shape 9% of NDVI variability, dominantly in semiarid shrublands. Assessing dominant timescales of vegetation-climate covariation, a natural surface classification emerges which captures patterns not represented by conventional classifications, especially in the tropics. Finally, we find that correlations between variables can differ and even invert signs across timescales. For southern Africa for example, correlation between NDVI and Tair is positive for the seasonal signal but negative for short-term and longer-term oscillations, indicating that both short- and long-term temperature anomalies can induce stress on vegetation dynamics. Such contrasting correlations between timescales exist for 15% of vegetated areas for NDVI with Tair and 27% with Prec, indicating global relevance of scale-specific climate sensitivities. Our analysis provides a detailed picture of vegetation-climate covariability globally, characterizing ecosystems by their intrinsic modes of temporal variability. We find that (i) correlations of NDVI with climate can differ between scales, (ii) nondominant subsignals in climate variables may dominate the biospheric response, and (iii) possible links may exist between short-term and longer-term scales. These heterogeneous ecosystem responses on different timescales may depend on climate zone and vegetation type, and they are to date not well understood and do not always correspond to transitions in dominant vegetation types. These scale dependencies can be a benchmark for vegetation model evaluation and for comparing remote sensing products.publishersversionpublishe

Outcome of Unilateral Pulmonary Edema after Minimal-Invasive Mitral Valve Surgery: 10-Year Follow-Up

The study was approved by the institutional review board (IRB) at the University Medical Center Campus Kiel, Kiel, Germany (reference number: AZ D 559/18) and registered at the German Clinical Trials Register (reference number: DRKS00022222). Objective Unilateral pulmonary edema (UPE) is a complication after minimally invasive mitral valve surgery (MIMVS). We analyzed the impact of this complication on the short- and long-term outcome over a 10-year period. Methods We retrospectively observed 393 MIMVS patients between 01/2009 and 12/2019. The primary endpoint was a radiographically and clinically defined UPE within the first postoperative 24 h, secondary endpoints were 30-day and long-term mortality and the percentage of patients requiring ECLS. Risk factors for UPE incidence were evaluated by logistic regression, and risk factors for mortality in the follow-up period were assessed by Cox regression. Results Median EuroSCORE II reached 0.98% in the complete MIMVS group. Combined 30-day and in-hospital mortality after MIMVS was 2.0% with a 95, 93 and 77% survival rate after 1, 3 and 10 years. Seventy-two (18.3%) of 393 patients developed a UPE 24 h after surgery. Six patients (8.3%) with UPE required an extracorporeal life-support system. Logistic regression analysis identified a higher creatinine level, a worse LV function, pulmonary hypertension, intraoperative transfusion and a longer aortic clamp time as predictors for UPE. Combined in hospital mortality and 30-day mortality was slightly but not significantly higher in the UPE group (4.2 vs. 1.6%; p = 0.17). Predictors for mortality during follow-up were age ≥ 70 years, impaired RVF, COPD, drainage loss ≥ 800 mL and length of ventilation ≥ 48 h. During a median follow-up of 4.6 years, comparable survival between UPE and non-UPE patients was seen in our analysis after 5 years (89 vs. 88%; p = 0.98)