Copper deficiency-associated myelopathy in cryptogenic hyperzincemia: A case report

Copper deficiency syndrome is an underestimated cause of posterior myelitis. We describe the case of a 41-year-old woman, who developed a subacute ataxic paraparesis associated with low back pain. Her 3T spine MRI showed a thin hyperintense FS-Echo T2 longitudinally extensive lesion involving the posterior columns of the cervical cord (from C2 to C6). An extensive diagnostic work-up excluded other causes of myelopathy and blood tests pointed out hypocupremia and mild hyperzincemia. Patients affected by this rare form of oligoelement deficiency typically develop progressive posterior column dysfunction with sensory ataxia and spasticity, sometimes associated with sensori-motor polyneuropathy. Clinical and radiological characteristics of posterior myelopathy due to copper deficiency are briefly reviewed. Physicians should be aware of this condition since a prompt introduction of copper supplementation can avoid progression of the neurological damage. (www.actabiomedica.it)

PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.

In the last years, dendritic cells (DC) have been evaluated for antitumor vaccination. Although DC-based vaccines have raised great expectations, their clinical translation has been largely disappointing. For these results, several explanations have been proposed. In particular, the concomitant expression by DCs of tolerogenic pathways, such as the immunosuppressive agent indoleamine 2,3-dioxygenase-1 (IDO1), has been demonstrated. The aim of this study is to evaluate both the stimulatory and the tolerogenic feature of monocyte-derived DCs (Mo-DCs) after maturation with PGE2. In particular, the role of IDO1 expression in PGE2-matured Mo-DCs has been addressed. Here we show that PGE2, which is required for full maturation of DCs, is one mediator of DC tolerance by enhancing IDO1. PGE2-mediated expression of IDO1 results in the production of kynurenine, in the generation of Tregs, and in the inhibition of either the allogeneic or the autologous antigen-specific stimulatory capacity of DCs. When pulsed with leukemic lysates and matured with PGE2, DCs are impaired in the induction of IFN-γ secreting CD4(+) and CD8(+) T cells due to IDO1 upregulation. Moreover, the inhibition of IDO1 enhances the antileukemic response. Overall, these results point toward the use of IDO1 inhibitors to enhance the vaccination capacity of DCs, matured with PGE2

p-TSA-Based DESs as “Active Green Solvents” for Microwave Enhanced Cyclization of 2-Alkynyl-(hetero)-arylcarboxylates: an Alternative Access to 6-Substituted 3,4-Fused 2-Pyranones

In this paper, we describe the use of p-TSA based Deep Eutectic Solvents (DESs) as alternative environmental-friendly \u201cactive\u201d solvents for the microwave-mediated synthesis of 6-substituted 3,4-fused 2-pyranones, and in particular isocoumarins, starting from 2-alkynyl-(hetero)arylcarboxylates. When the alkyne terminus bears a neutral or an electron-donating group (EDG), the reactions are fast, clean and highly regioselective, to give the 6-endo-dig cyclization products in good to excellent yields. For substrates bearing an electron-withdrawing group (EWG) on the alkyne end, the regioselectivity can be tuned by adding a small amount of silver(I) triflate as co-catalyst. DES was demonstrated to be reusable without loss of efficiency in terms of reaction yields. Based on experimental evidences and previous findings, two competitive mechanisms working simultaneously are proposed to explain the outcomes and the regioselectivity issues

Migración : Deriva- Puna (Salta)

Se estudió la relación migración - deriva en tres poblaciones puneñas (Cobres, Santa Rosa de los Pastos Grandes y Tolar Grande). Se construyeron las correspondientes matrices de migración progenitor - descendiente. Se partió de las frecuencias alélicas en 8 loci de grupos sanguíneos eritrocitarios (L*M, L*S, Di*B, P1, C, D, E y k) y se las proyectó 250 generaciones. Si bien las poblaciones estudiadas, desde el punto de vista de la demografía genética presentan coeficientes de aislamiento reproductivo que indican fuerte sujeción a la deriva (la migración efectiva no es suficiente para compensar los bajos efectivos poblacionales), con ayuda de este modelo se verifica que en muy pocas generaciones es factible llegar al equilibrio.Simposio: BiodemografíaAsociación de Antropología Biológica de la República Argentina (AABRA

Migración : Deriva- Puna (Salta)

Se estudió la relación migración - deriva en tres poblaciones puneñas (Cobres, Santa Rosa de los Pastos Grandes y Tolar Grande). Se construyeron las correspondientes matrices de migración progenitor - descendiente. Se partió de las frecuencias alélicas en 8 loci de grupos sanguíneos eritrocitarios (L*M, L*S, Di*B, P1, C, D, E y k) y se las proyectó 250 generaciones. Si bien las poblaciones estudiadas, desde el punto de vista de la demografía genética presentan coeficientes de aislamiento reproductivo que indican fuerte sujeción a la deriva (la migración efectiva no es suficiente para compensar los bajos efectivos poblacionales), con ayuda de este modelo se verifica que en muy pocas generaciones es factible llegar al equilibrio.Simposio: BiodemografíaAsociación de Antropología Biológica de la República Argentina (AABRA

Migración : Deriva- Puna (Salta)

Se estudió la relación migración - deriva en tres poblaciones puneñas (Cobres, Santa Rosa de los Pastos Grandes y Tolar Grande). Se construyeron las correspondientes matrices de migración progenitor - descendiente. Se partió de las frecuencias alélicas en 8 loci de grupos sanguíneos eritrocitarios (L*M, L*S, Di*B, P1, C, D, E y k) y se las proyectó 250 generaciones. Si bien las poblaciones estudiadas, desde el punto de vista de la demografía genética presentan coeficientes de aislamiento reproductivo que indican fuerte sujeción a la deriva (la migración efectiva no es suficiente para compensar los bajos efectivos poblacionales), con ayuda de este modelo se verifica que en muy pocas generaciones es factible llegar al equilibrio.Simposio: BiodemografíaAsociación de Antropología Biológica de la República Argentina (AABRA

Seasonal variability of the vitamin D effect on physical fitness in adolescents.

Studies investigating the relationship between vitamin D and physical fitness in youth have provided inconsistent findings. Recent evidence indicates that the expression of receptors and vitamin D-modulated genes in young subjects has a seasonal profile. Therefore, we investigated the role of vitamin D on physical fitness across seasons in a total of 977 male adolescents. Anthropometrics, lifestyle, dietary habits, biochemical profiles and physical fitness were studied. Multiple linear regression models, including pairwise interaction terms involving total 25-OH-vitamin D, were fitted. The interacting effect of season and total 25-OH-vitamin D had a significant influence on physical fitness performance (spring and total 25-OH-vitamin D: ß 0.19, SE 0.07, p = 0.007; summer and total 25-OH-vitamin D: ß 0.10, SE 0.06, p = 0.11; autumn and total 25-OH-vitamin D: ß 0.18, SE 0.07, p = 0.01), whereas the main effect of total 25-OH-vitamin D alone was not significant (p = 0.30). Body fat percentage, recreational physical activity level, time spent per day gaming/TV-watching, smoking, and hemoglobin levels were also related to the physical fitness performance score. Future studies should further explore the role of seasonal-dependent effects of vitamin D on health

The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.

Dendritic cells (DCs) are professional APCs that have a role in the initiation of adaptive immune responses and tolerance. Among the tolerogenic mechanisms, the expression of the enzyme IDO1 represents an effective tool to generate T regulatory cells. In humans, different DC subsets express IDO1, but less is known about the IDO1-related enzyme IDO2. In this study, we found a different pattern of expression and regulation between IDO1 and IDO2 in human circulating DCs. At the protein level, IDO1 is expressed only in circulating myeloid DCs (mDCs) and is modulated by PGE2, whereas IDO2 is expressed in both mDCs and plasmacytoid DCs and is not modulated by PGE2. In healthy subjects, IDO1 expression requires the presence of PGE2 and needs continuous transcription and translation, whereas IDO2 expression is constitutive, independent from suppressor of cytokine signaling 3 activity. Conversely, in patients suffering from inflammatory arthritis, circulating DCs express both IDO1 and IDO2. At the functional level, both mDCs and plasmacytoid DCs generate T regulatory cells through an IDO1/IDO2-dependent mechanism. We conclude that, in humans, whereas IDO1 provides an additional mechanism of tolerance induced by proinflammatory mediators, IDO2 is stably expressed in steady-state conditions and may contribute to the homeostatic tolerogenic capacity of DCs

c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells

Group-2 innate lymphoid cells (ILC2s), which are involved in type 2 inflammatory diseases such as allergy, can exhibit immunological memory, but the basis of this ILC2 "trained immunity" has remained unclear. Here, we found that stimulation with IL-33/IL-25 or exposure to the allergen papain induces the expression of the transcription factor c-Maf in mouse ILC2s. Chronic papain exposure results in high production of IL-5 and IL-13 cytokines and lung eosinophil recruitment, effects that are blocked by c-Maf deletion in ILCs. Transcriptomic analysis revealed that knockdown of c-Maf in ILC2s suppresses expression of type 2 cytokine genes, as well as of genes linked to a memory-like phenotype. Consistently, c-Maf was found highly expressed in human adult ILC2s but absent in cord blood and required for cytokine production in isolated human ILC2s. Furthermore, c-Maf-deficient mouse or human ILC2s failed to exhibit strengthened (“trained”) responses upon repeated challenge. Thus, the expression of c-Maf is indispensable for optimal type 2 cytokine production and proper memory-like responses in group-2 innate lymphoid cells

A Taxonomy of Causality-Based Biological Properties

We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this framework to a portion of a real metabolic pathway