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

ICAR: endoscopic skull‐base surgery

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Spatiotemporal network structure among "friends of friends" reveals contagious disease process.

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown

Spatiotemporal network structure among "friends of friends" reveals contagious disease process.

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown

Whole-genome analysis of mycobacteria from birds at the San Diego Zoo

<div><p>Methods</p><p>Mycobacteria isolated from more than 100 birds diagnosed with avian mycobacteriosis at the San Diego Zoo and its Safari Park were cultured postmortem and had their whole genomes sequenced. Computational workflows were developed and applied to identify the mycobacterial species in each DNA sample, to find single-nucleotide polymorphisms (SNPs) between samples of the same species, to further differentiate SNPs between as many as three different genotypes within a single sample, and to identify which samples are closely clustered genomically.</p><p>Results</p><p>Nine species of mycobacteria were found in 123 samples from 105 birds. The most common species were <i>Mycobacterium avium</i> and <i>Mycobacterium genavense</i>, which were in 49 and 48 birds, respectively. Most birds contained only a single mycobacterial species, but two birds contained a mixture of two species. The <i>M</i>. <i>avium</i> samples represent diverse strains of <i>M</i>. <i>avium avium</i> and <i>M</i>. <i>avium hominissuis</i>, with many pairs of samples differing by hundreds or thousands of SNPs across their common genome. By contrast, the <i>M</i>. <i>genavense</i> samples are much closer genomically; samples from 46 of 48 birds differ from each other by less than 110 SNPs. Some birds contained two, three, or even four genotypes of the same bacterial species. Such infections were found in 4 of 49 birds (8%) with <i>M</i>. <i>avium</i> and in 11 of 48 birds (23%) with <i>M</i>. <i>genavense</i>. Most were mixed infections, in which the bird was infected by multiple mycobacterial strains, but three infections with two genotypes differing by ≤ 10 SNPs were likely the result of within-host evolution. The samples from 31 birds with <i>M</i>. <i>avium</i> can be grouped into nine clusters within which any sample is ≤ 12 SNPs from at least one other sample in the cluster. Similarly, the samples from 40 birds with <i>M</i>. <i>genavense</i> can be grouped into ten such clusters. Information about these genomic clusters is being used in an ongoing, companion study of mycobacterial transmission to help inform management of bird collections.</p></div

Herpesvirus surveillance and discovery in zoo-housed ruminants.

Gammaherpesvirus infections are ubiquitous in captive and free-ranging ruminants and are associated with a variety of clinical diseases ranging from subclinical or mild inflammatory syndromes to fatal diseases such as malignant catarrhal fever. Gammaherpesvirus infections have been fully characterized in only a few ruminant species, and the overall diversity, host range, and biologic effects of most are not known. This study investigated the presence and host distribution of gammaherpesviruses in ruminant species at two facilities, the San Diego Zoo and San Diego Zoo Safari Park. We tested antemortem (blood, nasal or oropharyngeal swabs) or postmortem (internal organs) samples from 715 healthy or diseased ruminants representing 96 species and subspecies, using a consensus-based herpesvirus PCR for a segment of the DNA polymerase (DPOL) gene. Among the 715 animals tested, 161 (22.5%) were PCR and sequencing positive for herpesvirus, while only 11 (6.83%) of the PCR positive animals showed clinical signs of malignant catarrhal fever. Forty-four DPOL genotypes were identified of which only 10 have been reported in GenBank. The data describe viral diversity within species and individuals, identify host ranges of potential new viruses, and address the proclivity and consequences of interspecies transmission during management practices in zoological parks. The discovery of new viruses with wide host ranges and presence of co-infection within individual animals also suggest that the evolutionary processes influencing Gammaherpesvirus diversity are more complex than previously recognized

Mycobacterial species found by WGS in 123 samples from 105 birds.

<p>Mycobacterial species found by WGS in 123 samples from 105 birds.</p

Tree for 46 <i>M</i>. <i>genavense</i> samples.

<p>Each sample or subsample in one of the colored clusters is ≤ 12 SNPs from at least one other sample in the cluster. Although not shown on the tree, the bootstrap support values are between 97 and 100% for most but not all of the nodes outside of the colored clusters. Thus the overall tree topology is not quite as robust as that for the <i>M</i>. <i>avium</i> trees, presumably because the relevant branch lengths measured in SNPs are much shorter in the <i>M</i>. <i>genavense</i> tree.</p

Tree for 53 <i>M</i>. <i>avium</i> samples.

<p>Each sample or subsample in one of the colored clusters is ≤ 12 SNPs from at least one other sample in the cluster. The two clades above and below the arbitrary root have very different shapes. The upper clade is spread out with some samples separated from each other by nearly 10,000 SNPs. By contrast, the separation between the samples in the lower clade is much less and is better resolved in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173464#pone.0173464.g002" target="_blank">Fig 2</a>. Based on matches to the NCBI database, the 39 samples in the lower clade are all <i>M</i>. <i>avium avium</i>, while the 14 samples in the upper clade all seem to be <i>M</i>. <i>avium hominissuis</i>.</p

Concordance in species identification between WGS and conventional tests for 132 samples.

<p>Concordance in species identification between WGS and conventional tests for 132 samples.</p