Comparative Analysis of Serine/Arginine-Rich Proteins across 27 Eukaryotes: Insights into Sub-Family Classification and Extent of Alternative Splicing

Alternative splicing (AS) of pre-mRNA is a fundamental molecular process that generates diversity in the transcriptome and proteome of eukaryotic organisms. SR proteins, a family of splicing regulators with one or two RNA recognition motifs (RRMs) at the N-terminus and an arg/ser-rich domain at the C-terminus, function in both constitutive and alternative splicing. We identified SR proteins in 27 eukaryotic species, which include plants, animals, fungi and “basal” eukaryotes that lie outside of these lineages. Using RNA recognition motifs (RRMs) as a phylogenetic marker, we classified 272 SR genes into robust sub-families. The SR gene family can be split into five major groupings, which can be further separated into 11 distinct sub-families. Most flowering plants have double or nearly double the number of SR genes found in vertebrates. The majority of plant SR genes are under purifying selection. Moreover, in all paralogous SR genes in Arabidopsis, rice, soybean and maize, one of the two paralogs is preferentially expressed throughout plant development. We also assessed the extent of AS in SR genes based on a splice graph approach (http://combi.cs.colostate.edu/as/gmap_SRgenes). AS of SR genes is a widespread phenomenon throughout multiple lineages, with alternative 3′ or 5′ splicing events being the most prominent type of event. However, plant-enriched sub-families have 57%–88% of their SR genes experiencing some type of AS compared to the 40%–54% seen in other sub-families. The SR gene family is pervasive throughout multiple eukaryotic lineages, conserved in sequence and domain organization, but differs in gene number across lineages with an abundance of SR genes in flowering plants. The higher number of alternatively spliced SR genes in plants emphasizes the importance of AS in generating splice variants in these organisms

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Organisationskultur. Eine Konkretisierung aus systemtheoretischer Perspektive

Kühl S. Organisationskultur. Eine Konkretisierung aus systemtheoretischer Perspektive. Managementforschung. 2018;28(1):7-35.Die Bestimmung des Verhältnisses von Informalität und Organisationskultur bereitet in der Organisationstheorie Schwierigkeiten. Das liegt daran, dass der Begriff Informalität häufig stillschweigend durch den Begriff der Organisationskultur ersetzt wurde, ohne dass dafür eine präzise, abgrenzungsscharfe Definition vorgenommen worden wäre. Unter Rückgriff auf Überlegungen von Dario Rodríguez argumentiert dieser Artikel, dass die beiden Begriffe Organisationskultur und Informalität das gleiche Phänomen bezeichnen: die nichtentschiedenen Entscheidungsprämissen einer Organisation. Dabei wird systematisch zwischen „unentscheidbaren Entscheidungsprämissen“ und „prinzipiell entscheidbaren, aber nicht entschiedenen Entscheidungsprämissen“ unterschieden. Es wird gezeigt, wie sich mit einer präzisen Bestimmung über das Konzept der Entscheidungsprämissen Ordnung in die „wilden Merkmallisten“ der Literatur sowohl über Informalität als auch Organisationskultur bringen lässt und empirische Phänomene genauer erfasst werden können

Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS)

Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets

Tip-DC development during parasitic infection is regulated by IL-10 and requires CCL2/CCR2, IFN-gamma and MyD88 signaling.

The development of classically activated monocytic cells (M1) is a prerequisite for effective elimination of parasites, including African trypanosomes. However, persistent activation of M1 that produce pathogenic molecules such as TNF and NO contributes to the development of trypanosome infection-associated tissue injury including liver cell necrosis in experimental mouse models. Aiming to identify mechanisms involved in regulation of M1 activity, we have recently documented that during Trypanosoma brucei infection, CD11b(+)Ly6C(+)CD11c(+) TNF and iNOS producing DCs (Tip-DCs) represent the major pathogenic M1 liver subpopulation. By using gene expression analyses, KO mice and cytokine neutralizing antibodies, we show here that the conversion of CD11b(+)Ly6C(+) monocytic cells to pathogenic Tip-DCs in the liver of T. brucei infected mice consists of a three-step process including (i) a CCR2-dependent but CCR5- and Mif-independent step crucial for emigration of CD11b(+)Ly6C(+) monocytic cells from the bone marrow but dispensable for their blood to liver migration; (ii) a differentiation step of liver CD11b(+)Ly6C(+) monocytic cells to immature inflammatory DCs (CD11c(+) but CD80/CD86/MHC-II(low)) which is IFN-gamma and MyD88 signaling independent; and (iii) a maturation step of inflammatory DCs to functional (CD80/CD86/MHC-II(high)) TNF and NO producing Tip-DCs which is IFN-gamma and MyD88 signaling dependent. Moreover, IL-10 could limit CCR2-mediated egression of CD11b(+)Ly6C(+) monocytic cells from the bone marrow by limiting Ccl2 expression by liver monocytic cells, as well as their differentiation and maturation to Tip-DCs in the liver, showing that IL-10 works at multiple levels to dampen Tip-DC mediated pathogenicity during T. brucei infection. A wide spectrum of liver diseases associates with alteration of monocyte recruitment, phenotype or function, which could be modulated by IL-10. Therefore, investigating the contribution of recruited monocytes to African trypanosome induced liver injury could potentially identify new targets to treat hepatic inflammation in general, and during parasite infection in particular.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Assessment of a new questionnaire for self-reported sun sensitivity in an occupational skin cancer screening program

<p>Abstract</p> <p>Background</p> <p>Sun sensitivity of the skin is a risk factor for the development of cutaneous melanoma and other skin cancers. Epidemiological studies on causal factors for the development of melanoma must control for sun sensitivity as a confounder. A standardized instrument for measuring sun sensitivity has not been established yet. It is assumed that many studies show a high potential of residual confounding for sun sensitivity. In the present study, a new questionnaire for the assessment of self-reported sun sensitivity is administered and examined.</p> <p>Methods</p> <p>Prior to an occupational skin cancer screening program, the 745 participating employees were asked to fill in a questionnaire for self-assessment of sun sensitivity. The questionnaire was developed by experts of the working group "Round Table Sunbeds" (RTS) to limit the health hazards of sunbed use in Germany. A sun sensitivity score (RTS-score) was calculated using 10 indicators. The internal consistency of the questionnaire and the agreement with other methods (convergent validity) were examined.</p> <p>Results</p> <p>The RTS-score was calculated for 655 study participants who were 18 to 65 years of age. The correlation of the items among each other was between 0.12 and 0.62. The items and the RTS-score correlated between 0.46 and 0.77. The internal consistency showed a reliability coefficient with 0.82 (Cronbach's alpha). The comparison with the Fitzpatrick classification, the prevailing standard, was possible in 617 cases with a rank correlation of r_s= 0.65. The categorization of the RTS-score in four risk groups showed correct classification to the four skin types of Fitzpatrick in 75% of the cases. Other methods for the assessment of sun sensitivity displayed varying agreements with the RTS-score.</p> <p>Conclusion</p> <p>The RTS questionnaire showed a sufficient internal consistency. There is a good convergent validity between the RTS-score and the Fritzpatrick classification avoiding shortcomings of the prevailing standard. The questionnaire represents a simple, reliable and valid instrument for the assessment of sun sensitivity. The questionnaire can be useful for epidemiological studies as well as for skin cancer prevention. Further development and standardization of sun sensitivity assessments is necessary to strengthen the evidence of epidemiological studies on causal factors of melanoma and other skin cancers.</p

Macrophages and RhoA Pathway in Transplanted Organs

International audienceRhoA is a small GTPase that, via its downstream effectors, regulates a variety of cell functions such as cytokinesis, cell migration, vesicular trafficking, and phagocytosis. As such the RhoA pathway is also pivotal for proper functioning of immune cells including macrophages. By controlling actin cytoskeleton organization, RhoA pathway modulates macrophage's polarity and basic functions: phagocytosis, migration, and extracellular matrix degradation. Numerous studies indicate that macrophages are very important effectors contributing to acute and chronic rejection of transplanted organs. In this review we discuss the role of RhoA pathway in governance of macrophage's functions in terms of transplanted organs

Iron Metabolism: An Emerging Therapeutic Target in Critical Illness

Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901