Dietary iron depletion at weaning imprints low microbiome diversity and this is not recovered with oral nano Fe(III)

Alterations in the gut microbiota have been recently linked to oral iron. We conducted two feeding studies including an initial diet-induced iron-depletion period followed by supplementation with nanoparticulate tartrate-modified ferrihydrite (Nano Fe(III): considered bioavailable to host but not bacteria) or soluble ferrous sulfate (FeSO4: considered bioavailable to both host and bacteria). We applied denaturing gradient gel electrophoresis and fluorescence in situ hybridization for study-1 and 454-pyrosequencing of fecal 16S rRNA in study-2. In study-1, the within-community microbial diversity increased with FeSO4 (P = 0.0009) but not with Nano Fe(III) supplementation. This was confirmed in study-2, where we also showed that iron depletion at weaning imprinted significantly lower within- and between-community microbial diversity compared to mice weaned onto the iron-sufficient reference diet (P < 0.0001). Subsequent supplementation with FeSO4 partially restored the within-community diversity (P = 0.006 in relation to the continuously iron-depleted group) but not the between-community diversity, whereas Nano Fe(III) had no effect. We conclude that (1) dietary iron depletion at weaning imprints low diversity in the microbiota that is not, subsequently, easily recovered; (2) in the absence of gastrointestinal disease iron supplementation does not negatively impact the microbiota; and (3) Nano Fe(III) is less available to the gut microbiota.

Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents

Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and D-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.

Do soldiers' lives matter? A view from proportionality

A military operation is about to take place during an ongoing international armed conflict; it can be carried out either by aerial attack, which is expected to cause the deaths of enemy civilians, or by using ground troops, which is expected to cause the deaths of fewer enemy civilians but is expected to result in more deaths of compatriot soldiers. Does the principle of proportionality in international humanitarian law impose a duty on an attacker to expose its soldiers to life-threatening risks in order to minimise or avert risks of incidental damage to enemy civilians? If such a duty exists, is it absolute or qualified? And if it is a qualified duty, what considerations may be taken into account in determining its character and scope? This article presents an analytic framework under the current international humanitarian law (IHL) legal structure, following a proportionality analysis. The proposed framework identifies five main positions for addressing the above queries. The five positions are arranged along two ‘axes’: a value ‘axis’, which identifies the value assigned to the lives of compatriot soldiers in relation to lives of enemy civilians; and a justification ‘axis’, which outlines the justificatory bases for assigning certain values to lives of compatriot soldiers and enemy civilians: intrinsic, instrumental or a combination thereof. The article critically assesses these positions, and favours a position which attributes a value to compatriot soldiers’ lives, premised on a justificatory basis which marries intrinsic considerations with circumscribed instrumental considerations, avoiding the indeterminacy and normative questionability entailed by more expansive instrumental considerations.

Papal power and protection in the Shebet Yehudah

The sixteenth-century Shebet Yehudah is an account of the persecutions of Jews in various countries and epochs, including their expulsion from Spain in the fifteenth century. It is not a medieval text and was written long after many of the events it describes. Yet although it cannot give us a contemporary medieval standpoint, it provides important insights into how later Jewish writers perceived Jewish–papal relations in the thirteenth, fourteenth, and fifteenth centuries. Although the extent to which Jewish communities came into contact either with the papacy as an institution or the actions of individual popes varied immensely, it is through analysis of Hebrew works such as the Shebet Yehudah that we are able to piece together a certain understanding of Jewish ideas about the medieval papacy as an institution and the policies of individual popes. This article argues that Jews knew only too well that papal protection was not unlimited, but always carefully circumscribed in accordance with Christian theology. It is hoped that it will be a scholarly contribution to our growing understanding of Jewish ideas about the papacy's spiritual and temporal power and authority in the Later Middle Ages and how this impacted on Jewish communities throughout medieval Europe.