Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting.

Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons.

Dietary selenium in adjuvant therapy of viral and bacterial infections.

Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions.

Towards identifying novel anti-Eimeria agents: trace elements, vitamins, and plant-based natural products.

Eimeriosis, a widespread infectious disease of livestock, is caused by coccidian protozoans of the genus Eimeria. These obligate intracellular parasites strike the digestive tract of their hosts and give rise to enormous economic losses, particularly in poultry, ruminants including cattle, and rabbit farming. Vaccination, though a rational prophylactic measure, has not yet been as successful as initially thought. Numerous broad-spectrum anti-coccidial drugs are currently in use for treatment and prophylactic control of eimeriosis. However, increasing concerns about parasite resistance, consumer health, and environmental safety of the commercial drugs warrant efforts to search for novel agents with anti-Eimeria activity. This review summarizes current approaches to prevent and treat eimeriosis such as vaccination and commercial drugs, as well as recent attempts to use dietary antioxidants as novel anti-Eimeria agents. In particular, the trace elements selenium and zinc, the vitamins A and E, and natural products extracted from garlic, barberry, pomegranate, sweet wormwood, and other plants are discussed. Several of these novel anti-Eimeria agents exhibit a protective role against oxidative stress that occurs not only in the intestine of Eimeria-infected animals, but also in their non-parasitized tissues, in particular, in the first-pass organ liver. Currently, it appears to be promising to identify safe combinations of low-cost natural products with high anti-Eimeria efficacy for a potential use as feed supplementation in animal farming.

Dietary selenium affects intestinal development of Eimeria papillata in mice.

Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The prepatent period lasts for 3 days, but the course of infections varied. At Se-adequate diet, the maximum fecal output of oocysts amounted to 68,300 ooccysts/g feces on day 5 p.i.. However, fecal shedding of oocysts was accelerated in mice on Se-deficient diet and occurred already on day 4 p.i.. By contrast, maximal shedding is impaired in mice on high-Se diet, which takes place on day 5 p.i., but with a decreased output of only 7,300 oocysts/g feces. Light microscopy reveals that all developmental stages are affected: meronts, micro- and macrogamonts, and developing oocysts are increased in comparison with mice fed on selenium-adequate diet. At high Se, the number of parasitic stages in the jejunum is substantially higher than at Se-deficient diet. Se does not affect the number of jejunal Alcian blue-stained goblet cells. Se deficiency increased the number of apoptotic cells in the jejunum. Substantially increased histological injury scores reveal more injuries in jejunum tissue infected by E. papillata. Our data indicate that high dietary Se exerts potential anticoccidial activity. This may be taken advantage of in control measures towards Eimeriosis as a feed additive, potentially alleviating the need for concomitantly utilized anti-coccidial drugs in the feed.

Differential miRNA expression in the mouse jejunum during garlic treatment of Eimeria papillata infections.

Accumulating evidence indicates a critical role of microRNAs (miRNAs) in the outcome of diseases. Here, we investigate the effect of garlic on the intestinal miRNA signature of male Balb/c mice during infections with Eimeria papillata. Garlic decreases the intracellular development as evidenced by a lowered fecal output of E. papillata oocysts from 3,150 ± 410 to approximately 1,750 ± 390 oocysts per gram feces on day 4 postinoculation. This anti-coccidial activity of garlic is associated with an inhibition of the E. papillata-induced increases of interferon gamma, inducible nitric oxide synthase, nitrite/nitrate, and malondialdehyde and decrease in glutathione. Moreover, garlic downregulates the E. papillata-induced increases in the expression of the miRNAs miR-1959, miR-203, and miR-21, and it upregulates the expression of the 11 miRNA species miR-142-5P, miR-15A, miR-10A, miR-29B, miR-1902, miR-125A-5P, let-7E, miR-148A, miR-130A, miR-10B, and miR-93, respectively, as revealed by miRXplore microarray technology. Real-time PCR confirms these effects of garlic in the jejunum of E. papillata-infected mice. Our data indicate that the anti-coccidial activity of garlic is associated with specific changes in the miRNA signature of the mouse jejunum, the target site of E. papillata. These changes may reflect an involvement of miRNAs in garlic-activated pathways to reduce and/or to repair E. papillata-induced tissue injuries.

Cadmium resistance conferred to yeast by a non-metallothionein-encoding gene of the earthworm Enchytraeus.

The earthworm Enchytraeus is able to survive in cadmium (Cd)-polluted environments. Upon Cd exposure, the worms express a gene encoding the putative non-metallothionein 25-kDa cysteine-rich protein (CRP), which contains eight repeats with highly conserved cysteines in Cys-X-Cys and Cys-Cys arrangements exhibiting 36-53% identities to the 6-7-kDa metallothioneins of different organisms. Here, we demonstrate that the CRP protein confers a highly Cd-resistant phenotype to a Cd-hypersensitive yeast strain. Cd resistance increases with increasing numbers of expressed CRP repeats, but even one 3-kDa CRP repeat still mediates Cd resistance. Site-directed mutagenesis reveals that each single cysteine within a given repeat is important for Cd resistance, though to a different extent. However, replacement of other conserved amino acids such as Pro(136) and Asp(196) at the CRP repeat junctions does not affect Cd resistance. Our data indicate (i) that the non-metallothionein CRP protein is able to detoxify Cd and (ii) that this is dependent on the availability of sulfhydryl groups of the conserved cysteines.