The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Modulation of systemic immune responses through commensal gastrointestinal microbiota.

Colonization of the gastrointestinal (GI) tract is initiated during birth and continually seeded from the individual's environment. Gastrointestinal microorganisms play a central role in developing and modulating host immune responses and have been the subject of investigation over the last decades. Animal studies have demonstrated the impact of GI tract microbiota on local gastrointestinal immune responses; however, the full spectrum of action of early gastrointestinal tract stimulation and subsequent modulation of systemic immune responses is poorly understood. This study explored the utility of an oral microbial inoculum as a therapeutic tool to affect porcine systemic immune responses. For this study a litter of 12 pigs was split into two groups. One group of pigs was inoculated with a non-pathogenic oral inoculum (modulated), while another group (control) was not. DNA extracted from nasal swabs and fecal samples collected throughout the study was sequenced to determine the effects of the oral inoculation on GI and respiratory microbial communities. The effects of GI microbial modulation on systemic immune responses were evaluated by experimentally infecting with the pathogen Mycoplasma hyopneumoniae. Coughing levels, pathology, toll-like receptors 2 and 6, and cytokine production were measured throughout the study. Sequencing results show a successful modulation of the GI and respiratory microbiomes through oral inoculation. Delayed type hypersensitivity responses were stronger (p = 0.07), and the average coughing levels and respiratory TNF-α variance were significantly lower in the modulated group (p<0.0001 and p = 0.0153, respectively). The M. hyopneumoniae infection study showed beneficial effects of the oral inoculum on systemic immune responses including antibody production, severity of infection and cytokine levels. These results suggest that an oral microbial inoculation can be used to modulate microbial communities, as well as have a beneficial effect on systemic immune responses as demonstrated with M. hyopneumoniae infection

Differences in within group similarity for GI and respiratory microbiome samples at multiple time points.

<p>Boxplots showing no significant difference for within group similarity of the GI microbial communities A) for multiple time points before oral inoculation, B) significant differences for within group similarity (<i>p</i> = 0.0016) and variation (<i>p</i> = 0.0038) one day after completion of the oral inoculation (40 days of age) and C) significant differences for within group similarity (<i>p</i> = 0.0024) and variation (<i>p</i><0.0001) for all time points following oral inoculation. D) Boxplots showing differences for within group similarity (<i>p</i> = 0.063) and variation (<i>p</i> = 0.0006) of the respiratory microbial communities for all time points following oral inoculation. ** denotes statistical significance of <i>p</i><0.005.</p

Summary of host responses.

<p>Summary of host responses.</p

Differences in macroscopic lung lesion scores of pigs infected with <i>M. hyopneumoniae.</i>

<p>The lungs were removed at euthanasia (35 dpi) and evaluated blindly. Expressed as percentage of lungs with lesions (<i>p</i> = 0.07).</p

Seropositivity to <i>M. hyopneumoniae.</i>

<p>Days post infection with <i>M. hyopneumoniae</i>. Seropositivity denotes number of animals with <i>M. hyopneumoniae</i> antibodies present in blood serum (6 animals/group).</p