Age-associated systemic factors change central and peripheral immunity in adult male mice.

Aging coincides with major changes in brain immunity that aid in a decline in neuronal function. Here, we postulate that systemic, pro-aging factors contribute to immunological changes that occur within the brain during aging. To investigate this hypothesis, we comprehensively characterized the central and peripheral immune landscape of 20-month-old male mice using cytometry by time-of-flight (CyTOF) and investigated the role of age-associated circulating factors. We found that CD8+ T cells expressing programmed cell death protein 1 (PD1) and tissue-resident memory CD8+ T cells accumulated in the aged brain while levels of memory T cells rose in the periphery. Injections of plasma derived from 20-month-old mice into 5-month-old receiving mice decreased the frequency of splenic and circulating naïve T cells, increased memory CD8+ T cells, and non-classical, patrolling monocytes in the spleen, and elevated levels of regulatory T cells and non-classical monocytes in the blood. Notably, CD8+ T cells accumulated within white matter areas of plasma-treated mice, which coincided with the expression of vascular cell adhesion molecule 1 (VCAM-1), a mediator of immune cell trafficking, on the brain vasculature. Taken together, we here describe age-related immune cell changes in the mouse brain and circulation and show that age-associated systemic factors induce the expansion of CD8+ T cells in the aged brain.

A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. OBJECTIVES: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. METHODS: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. RESULTS: Interleukin (IL)-1ß, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P < 0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin type II but not in skin type VI. Skin type VI showed higher NMF levels in both nonlesional and lesional AD skin than skin type II. Corneocyte morphology was significantly different in lesional AD skin compared with nonlesional AD and healthy skin. CONCLUSIONS: Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types.

[Cow's milk allergy]. / Koemelkallergie.

Cow's milk allergy is the most common food allergy among children. Patients with cow's milk allergy may present a wide range of complaints. Complaints can occur in multiple organ systems. The gold standard to confirm a diagnosis of cow's milk allergy is the double-blind placebo-controlled food challenge. The treatment consists of the elimination of cow's milk from a child's diet.It is estimated that at the age of 1 year, 75% of children with cow's milkallergy have become tolerant to cow's milk, and 90% at the age of 4 years. It is recommended to expose all infants with cow's milk allergy to cow's milk at the age of 1 year to see if they have become tolerant.

Distinct phosphatase activity profiles in two strains of Trypanosoma cruzi.

Phosphorylation of parasite proteins plays a key role in the process of cell invasion by Trypanosoma cruzi, the etiologic agent of Chagas' disease. In this sense, characterization of parasite kinases and phosphatases could open new possibilities for the rational design of chemotherapeutic agents for the treatment of Chagas' disease. In this work, we analyzed phosphatase activities in T. cruzi homogenates from 2 strains belonging to different lineages and with different resistance to oxidative stress. Tulahuen 2 cells (Lineage I) showed higher phosphatase activities and specificity constants when compared to the Y strain (Lineage II). Tulahuen 2 had an optimum phosphatase activity at pH 4.0 and the Y strain at pH 7.0. In both cases, neutral­basic, but not acid, phosphatase activities were increased in the presence of Mg2+. Although calcium had an inhibitory effect at a pH of 7.0 and 8.0 in the Y strain, this inhibition was restricted to pH 8.0 in the other strain. Different substrates and acid phosphotyrosine and alkaline phosphatase inhibitors exhibited distinct effects on the phosphatase activity of both strains. Our results provide a better understanding of T. cruzi phosphatases and reinforce the notion of heterogeneity among T. cruzi populations.

Chiral polymers by iterative tandem catalysis.

Racemic omega-substituted caprolactones can be completely converted into chiral polyesters of remarkable MW and high ee by combining lipase-catalyzed ring-opening polymerization with Ru-catalyzed racemization.