Translational implications of Th17-skewed inflammation due to genetic deficiency of a cadherin stress sensor

Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1–/– skin showed a delay in expression of adhesion/differentiation/ keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17–skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1–/– mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients

Phosphorylation Alters the Interaction of the Arabidopsis Phosphotransfer Protein AHP1 with Its Sensor Kinase ETR1

The ethylene receptor ethylene response 1 (ETR1) and the Arabidopsis histidine-containing phosphotransfer protein 1 (AHP1) form a tight complex in vitro. According to our current model ETR1 and AHP1 together with a response regulator form a phosphorelay system controlling the gene expression response to the plant hormone ethylene, similar to the two-component signaling in bacteria. The model implies that ETR1 functions as a sensor kinase and is autophosphorylated in the absence of ethylene. The phosphoryl group is then transferred onto a histidine at the canonical phosphorylation site in AHP1. For phosphoryl group transfer both binding partners need to form a tight complex. After ethylene binding the receptor is switched to the non-phosphorylated state. This switch is accompanied by a conformational change that decreases the affinity to the phosphorylated AHP1. To test this model we used fluorescence polarization and examined how the phosphorylation status of the proteins affects formation of the suggested ETR1−AHP1 signaling complex. We have employed various mutants of ETR1 and AHP1 mimicking permanent phosphorylation or preventing phosphorylation, respectively. Our results show that phosphorylation plays an important role in complex formation as affinity is dramatically reduced when the signaling partners are either both in their non-phosphorylated form or both in their phosphorylated form. On the other hand, affinity is greatly enhanced when either protein is in the phosphorylated state and the corresponding partner in its non-phosphorylated form. Our results indicate that interaction of ETR1 and AHP1 requires that ETR1 is a dimer, as in its functional state as receptor in planta

DNA Methods to Identify Missing Persons

Human identification by DNA analysis in missing person cases typically involves comparison of two categories of sample: a reference sample, which could be obtained from intimate items of the person in question or from family members, and the questioned sample from the unknown person-usually derived from the bones, teeth, or soft tissues of human remains. Exceptions include the analysis of archived tissues, such as those held by hospital pathology departments, and the analysis of samples relating to missing, but living persons. DNA is extracted from the questioned and reference samples and well-characterized regions of the genetic code are amplified from each source using the Polymerase Chain Reaction (PCR), which generates sufficient copies of the target region for visualization and comparison of the genetic sequences obtained from each sample. If the DNA sequences of the questioned and reference samples differ, this is normally sufficient for the questioned DNA to be excluded as having come from the same source. If the sequences are identical, statistical analysis is necessary to determine the probability that the match is a consequence of the questioned sequence coming from the same individual who provided the reference sample or from a randomly occurring individual in the general population. Match probabilities that are currently achievable are frequently greater than 1 in 1 billion, allowing identity to be assigned with considerable confidence in many cases

Effect of Fertilization on Native Grass Pastures in Oklahoma

This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

The Evolution of Systems of Care for Children\u27s Mental Health: Forty Years of Community Child and Adolescent Psychiatry

Over the past 20 years, child and adolescent community mental health has evolved conceptually, clinically, and scientifically towards the community-based systems of care model. This model asserts important values and principles, including the centrality of the child and family in the care process, the integration of the efforts of disparate agencies and interveners into a contextual approach, and the importance of serving children with serious disturbances in their homes and communities. The article reviews the evolution of the community-based systems of care model, its evidence-base, its application in practice, and the challenges it faces in today\u27s human services environment

Forage Crops Evaluation and Management Studies Progress Report, 1953

The Oklahoma Agricultural Experiment Station periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

Forage Crops Evaluation and Management Studies Progress Report, 1955

The Oklahoma Agricultural Experiment Station periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed by dendritic cells

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