Year in review 2007: Critical Care – shock

The research papers on shock published in Critical Care throughout 2007 are related to three major subjects: the modulation of the macrocirculation and microcirculation during shock, focusing on arginine vasopressin, erythropoietin and nitric oxide; studies on metabolic homeostasis (acid–base status, energy expenditure and gastrointestinal motility); and basic supportive measures in critical illness (fluid resuscitation and sedation, and body-temperature management). The present review summarizes the key results of these studies and provides a brief discussion in the context of the relevant scientific and clinical background

How T Cells Do the “Search for the Needle in the Haystack”

In the body, a T cell is confronted with millions of antigen-presenting cells (APCs) in the search for potentially harmful antigen. To elicit an appropriate immune response, this search has to be performed as fast and as precise as possible. These two requirements, however, are at odds with each other: fast searches lack accuracy, whereas high fidelity decisions are typically time-consuming. Here, we use the archetypical search for the needle in the haystack as an analogy for the T cell's search problem. We provide a statistical framework to quantitatively estimate the constraints of search strategies for rare instances. Particularly, we propose a solution for balancing the demand for high speed with low error rates. It takes advantage of a two-phase search process, which combines a first rapid scan with a second high-fidelity check. Finally, we provide arguments that support a two-phase search model for identification of antigen-positive APCs by T cells

RNF40 regulates gene expression in an epigenetic context-dependent manner

Background Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-“suppressed” genes is associated with enhancer activation via FOXL2. Conclusion Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?

Background Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms. Objective The objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVID Design A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE ( via Pubmed) and Web of Science. Results The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome’s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population. Conclusions Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies

Pengembangan Kurikulum Pendidikan Lingkungan di Kota Tangerang Selatan: Bagaimana Mengintegrasikan Deklarasi Tbilisi dalam Kurikulum

This study aims to develop environmental education curriculum based on Tbilisi Declaration. There were five environmental education goals of Tbilisi Declaration namely knowledge, awareness, attitudes, skills, and participation. Curriculum was developed for supporting education policy in South Tangerang, Banten Province, Indonesia. Letter of Education Division South Tangerang City nomor 800/KEP 1222-dikdas/2014 stated environmental education as local curriculum in South Tangerang Elementary School. Curriculum was developed by developmental research. There was four steps to develop curriculum, every steps had three activities, i.e. making, reviewing, and fixing. This study result some standard and basic competences. Research developed environmental education was integrated with thematic subject matter in 1st and 2nd grade, but as monolithic subject matter in 3rd – 6rd grade. Using exiting competence standard from 2014 curriculum and format standard competence 2006 made this curriculum have flexibility to implement for the school that used 2006 or 2013 curriculum

Homo- and Heteroassociations Drive Activation of ErbB3

L

Light inactivation of water transport and protein–protein interactions of aquaporin–Killer Red chimeras

Aquaporins (AQPs) have a broad range of cellular and organ functions; however, nontoxic inhibitors of AQP water transport are not available. Here, we applied chromophore-assisted light inactivation (CALI) to inhibit the water permeability of AQP1, and of two AQP4 isoforms (M1 and M23), one of which (M23) forms aggregates at the cell plasma membrane. Chimeras containing Killer Red (KR) and AQPs were generated with linkers of different lengths. Osmotic water permeability of cells expressing KR/AQP chimeras was measured from osmotic swelling–induced dilution of cytoplasmic chloride, which was detected using a genetically encoded chloride-sensing fluorescent protein. KR-AQP1 red fluorescence was bleached rapidly (∼10% per second) by wide-field epifluorescence microscopy. After KR bleaching, KR-AQP1 water permeability was reduced by up to 80% for the chimera with the shortest linker. Remarkably, CALI-induced reduction in AQP4-KR water permeability was approximately twice as efficient for the aggregate-forming M23 isoform; this suggests intermolecular CALI, which was confirmed by native gel electrophoresis on cells coexpressing M23-AQP4-KR and myc-tagged M23-AQP4. CALI also disrupted the interaction of AQP4 with a neuromyelitis optica autoantibody directed against an extracellular epitope on AQP4. CALI thus permits rapid, spatially targeted and irreversible reduction in AQP water permeability and interactions in live cells. Our data also support the utility of CALI to study protein–protein interactions as well as other membrane transporters and receptors

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?

BackgroundRecovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.ObjectiveThe objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVIDDesignA systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.ResultsThe literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome’s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.ConclusionsPersistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies