We investigate the swampland distance conjecture (SDC) in the complex moduli space of type II compactifications on one-parameter Calabi-Yau threefolds. This class of manifolds contains hundreds of examples and, in particular, a subset of 14 geometries with hypergeometric differential Picard-Fuchs operators. Of the four principal types of singularities that can occur -specified by their limiting mixed Hodge structure -only the K-points and the large radius points (or more generally the M -points) are at infinite distance and therefore of interest to the SDC. We argue that the conjecture is fulfilled at the K-and the M -points, including models with several M -points, using explicit calculations in hypergeometric models which contain typical examples of all these degenerations. Together with previous work on the large radius points, this suggests that the SDC is indeed fulfilled for one-parameter Calabi-Yau spaces.

Introduction: Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (HED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a HED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. Objetives: The aim of this study was to investigate the effect of long-term (6 months) consumption of HED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the nucleus of the solitary tract, and systemic inflammation. Methods: Male Sprague-Dawley rats were fed a low energy density (LED) diet for 2 weeks and then switched to a HED diet for 26 weeks. Twenty-four-hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, 1, 4, 8, and 26 weeks after introduction of the HED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were assessed for 16 S rRNA genome sequencing. Results: HED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after 4 weeks of HED diet. We further observed changes in the serum cytokine profile after 26 weeks of HED feeding. Conclusions: These data suggest that microbiota dysbiosis is the first response of the organism to HED diets, followed by increased liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers. To our knowledge, this is the first study to present longitudinal and cross-sectional results on effect of long-term consumption of HED diets on all these parameters in a single cohort of animals.

BCL10/MALT1 signaling in keratinocytes is altered in human sporadic psoriasis and is a critical initiator and amplifier of skin inflammation in mouse models.

Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (ED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a high ED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. The aim of the current study was to investigate the effect of long-term (6 months) consumption of high ED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the Nucleus of the Solitary Tract, and the development of systemic inflammation. Male Sprague-Dawley rats were fed a low ED diet (5% fat) for two weeks and then switched to a high ED (45% fat) diet for 26 weeks. Twenty-four hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, and 1, 4, 8, and 26 weeks after introduction of the high ED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were used for 16S rRNA genome sequencing. High ED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after four weeks of high ED diet. We further observed changes in the serum cytokine profile after 26 weeks of high ED feeding. These data suggest that microbiota dysbiosis is the first response of the organism to high ED diets and this, in turn, detrimentally affects liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers.