There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5′-UTR and 3′-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.

Objective To evaluate the association of subretinal hyper-reflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar in the Comparison of Age related Macular Degeneration Treatments Trials (CATT) Design Prospective cohort study within a randomized clinical trial. Participants The 1185 participants in CATT. Methods Participants were randomly assigned to ranibizumab or bevacizumab treatment monthly or as-needed. Masked readers graded scar and GA on fundus photography and fluorescein angiography images, SHRM on time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1mm2, or outside the center 1mm2 were obtained on SD-OCT images at 56 (n=76) and 104 (n=66) weeks. VA was measured by certified examiners. Main Outcome Measures SHRM presence, location and size, and associations with VA, scar, and GA. Results Among all CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than eyes with SHRM that resolved (64% vs. 31%; p<0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n=76) and 104 (n=66), mean [SE] VA letter score was 73.5 [2.8], 73.1 [3.4], 65.3 [3.5], and 63.9 [3.7] when SHRM was absent, present outside the central 1mm2, present within the central 1mm2 but not the foveal center, or present at the foveal center (p=0.02). SHRM was present at the foveal center in 43 (30%), within the central 1mm2 in 21 (15%) and outside the central 1mm2 in 19 (13%). When SHRM was present, the median maximum height in microns under the fovea, within the central 1 mm2 including the fovea and anywhere within the scan was 86; 120; and 122, respectively. VA was decreased with greater SHRM height and width (p<0.05). Conclusions SHRM is common in eyes with NVAMD and often persists after anti-VEGF treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM height and width were associated with worse VA. SHRM is an important morphological biomarker in eyes with NVAMD.

BackgroundA variety of bacteria are known to influence carcinogenesis. Therefore, we sought to investigate if publicly available whole genome and whole transcriptome sequencing data generated by large public cancer genome efforts, like The Cancer Genome Atlas (TCGA), could be used to identify bacteria associated with cancer. The Burrows-Wheeler aligner (BWA) was used to align a subset of Illumina paired-end sequencing data from TCGA to the human reference genome and all complete bacterial genomes in the RefSeq database in an effort to identify bacterial read pairs from the microbiome.ResultsThrough careful consideration of all of the bacterial taxa present in the cancer types investigated, their relative abundance, and batch effects, we were able to identify some read pairs from certain taxa as likely resulting from contamination. In particular, the presence of Mycobacterium tuberculosis complex in the ovarian serous cystadenocarcinoma (OV) and glioblastoma multiforme (GBM) samples was correlated with the sequencing center of the samples. Additionally, there was a correlation between the presence of Ralstonia spp. and two specific plates of acute myeloid leukemia (AML) samples. At the end, associations remained between Pseudomonas-like and Acinetobacter-like read pairs in AML, and Pseudomonas-like read pairs in stomach adenocarcinoma (STAD) that could not be explained through batch effects or systematic contamination as seen in other samples.ConclusionsThis approach suggests that it is possible to identify bacteria that may be present in human tumor samples from public genome sequencing data that can be examined further experimentally. More weight should be given to this approach in the future when bacterial associations with diseases are suspected.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0224-8) contains supplementary material, which is available to authorized users.

The 22 February 2011, Mw6.2-6.3 Christchurch earthquake is the most costly earthquake to affect New Zealand, causing 181 fatalities and severely damaging thousands of residential and commercial buildings, and most of the city lifelines and infrastructure. This manuscript presents an overview of observed geotechnical aspects of this earthquake as well as some of the completed and on-going research investigations. A unique aspect, which is particularly emphasized, is the severity and spatial extent of liquefaction occurring in native soils. Overall, both the spatial extent and severity of liquefaction in the city was greater than in the preceding 4th September 2010 Darfield earthquake, including numerous areas that liquefied in both events. Liquefaction and lateral spreading, variable over both large and short spatial scales, affected commercial structures in the Central Business District (CBD) in a variety of ways including: total and differential settlements and tilting; punching settlements of structures with shallow foundations; differential movements of components of complex structures; and interaction of adjacent structures via common foundation soils. Liquefaction was most severe in residential areas located to the east of the CBD as a result of stronger ground shaking due to the proximity to the causative fault, a high water table approximately 1m from the surface, and soils with composition and states of high susceptibility and potential for liquefaction. Total and differential settlements, and lateral movements, due to liquefaction and lateral spreading is estimated to have severely compromised 15,000 residential structures, the majority of which otherwise sustained only minor to moderate damage directly due to inertial loading from ground shaking. Liquefaction also had a profound effect on lifelines and other infrastructure, particularly bridge structures, and underground services. Minor damage was also observed at flood stop banks to the north of the city, which were more severely impacted in the 4th September 2010 Darfield earthquake. Due to the large high-frequency ground motion in the Port hills numerous rock falls and landslides also occurred, resulting in several fatalities and rendering some residential areas uninhabitable.

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Lateral gene transfer (LGT) from bacteria to animals occurs more frequently than was appreciated prior to the advent of genome sequencing. In 2007, LGT from bacterial Wolbachia endosymbionts was detected in ∼33% of the sequenced arthropod genomes using a bioinformatic approach. Today, Wolbachia/host LGT is thought to be widespread and many other cases of bacteria-animal LGT have been described. In insects, LGT may be more frequently associated with endosymbionts that colonize germ cells and germ stem cells, like Wolbachia endosymbionts. We speculate that LGT may occur from bacteria to a wide variety of eukaryotes, but only becomes vertically inherited when it occurs in germ cells. As such, LGT may happen routinely in somatic cells but never become inherited or fixed in the population. Lack of inheritance of such mutations greatly decreases our ability to detect them. In this review, we propose that such noninherited bacterial DNA integration into chromosomes in human somatic cells could induce mutations leading to cancer or autoimmune diseases in a manner analogous to mobile elements and viral integrations.

In the 4 September 2010 (M W 07.1) and 22 February 2011 (M W 06.2) earthquakes, widespread liquefaction and lateral spreading occurred throughout Christchurch and the town of Kaiapoi. The severe soil liquefaction and lateral spreading in particular caused extensive and heavy damage to residential buildings, Christchurch business district (CBD) buildings, bridges and water supply and wastewater systems of Christchurch. After the earthquake, comprehensive field investigations and inspections were conducted to document the liquefaction-induced land damage and lateral spreading displacements and their impact on buildings and infrastructure. The results of ground surveying measurements of lateral spreads at approximately 120 locations along the Avon River, Kaiapoi River and streams in the affected area reveal permanent lateral ground displacements at the banks of up to 2Á3 m that progressed inland as far as 200Á250 m from the waterway, causing significant damage to structures located within the spreading zone. Different features and magnitudes of spreading were identified, which were often affected by a complex interplay of ground conditions, topography, meandering river geometry and local depositional environment. The spreading was characterised by very large and highly non-uniform ground deformation causing stretching of building foundations and the buildings themselves. Road bridges suffered a characteristic spreading-induced damage mechanism including back-rotation of the abutments associated with deck pinning and damage at the top of the abutment piles. The wastewater system of Christchurch was hit particularly hard by the liquefaction and lateral spreading, and approximately 60% of the damaged pipes of the potable water system were located in areas of severe liquefaction and lateral spreading.

This paper discusses the performance of road bridges during the 2010–2011 Canterbury earthquakes and focuses on the response of bridges in liquefying soils undergoing lateral spreading. A characteristic spreading-induced mechanism for short-span bridges with rigid superstructures is presented and explored using four well-documented case studies. A series of pseudo-static analyses are then used to investigate the observed response of the bridges and their pile foundations in particular. Deformations and damage to the piles are evaluated and correlated with the spreading displacements, and key factors controlling the pile response and the development of the spreading-induced damage mechanism are identified.