Antigen Diversity in the Parasitic Bacterium Anaplasma phagocytophilum Arises from Selectively-Represented, Spatially Clustered Functional Pseudogenes

Anaplasma phagocytophilum is a tick-transmitted bacterial pathogen of humans and other animals, and is an obligate intracellular parasite. Throughout the course of infection, hosts acquire temporary resistance to granulocytic anaplasmosis as they develop immunity specific for the major antigen, major surface protein 2 (Msp2). However, the bacterium then utilizes a novel recombination mechanism shuffling functional pseudogenes sequentially into an expression cassette with conserved 5′ and 3′ ends, bypassing host immunity. Approximately 100 pseudogenes are present in the only fully sequenced human-origin HZ genome, representing the possibility for almost unlimited antigenic diversity. In the present study, we identified a select group of 20% of the A. phagocytophilum HZ msp2 pseudogenes that have matched preferentially to human, canine, and equine expression cassettes. Pseudogenes cluster predominantly in one spatial run limited to a single genomic island in less than 50% of the genome but phylogenetically related pseudogenes are neither necessarily located in close proximity on the genome nor share similar percent identity with expression cassettes. Pseudogenes near the expression cassette (and the origin) are more likely to be expressed than those farther away. Taken together, these findings suggest that there may be natural selection pressure to retain pseudogenes in one cluster near the putative origin of replication, even though global recombination shuffles pseudogenes around the genome, separating pseudogenes that share genetic origins as well as those with similar identities

Managing Opportunities and Challenges of Co-Authorship

Research with the largest impact on practice and science is often conducted by teams with diverse substantive, clinical, and methodological expertise. Team and interdisciplinary research has created authorship groups with varied expertise and expectations. Co-authorship among team members presents many opportunities and challenges. Intentional planning, clear expectations, sensitivity to differing disciplinary perspectives, attention to power differentials, effective communication, timelines, attention to published guidelines, and documentation of progress will contribute to successful co-authorship. Both novice and seasoned authors will find the strategies identified by the Western Journal of Nursing Research Editorial Board useful for building positive co-authorship experiences

Effects of Drought and the Emergency Drought Barrier on the Ecosystem of the California Delta

In 2015, the fourth year of the recent drought, the California Department of Water Resources installed a rock barrier across False River west of Franks Tract to limit salt intrusion into the Delta at minimal cost in freshwater. This Barrier blocked flow in False River, greatly reducing landward salt transport by decreasing tidal dispersion in Franks Tract. We investigated some ecological consequences of the Barrier, examining its effects on water circulation and exchange, on distributions of submerged aquatic vegetation (SAV) and bivalves, and on phytoplankton and zooplankton. The Barrier allowed SAV to spread to areas of Franks Tract that previously had been clear. The distributions of bivalves (Potamocorbula and Corbicula) responded to the changes in salinity at time–scales of months for newly settled individuals, to 1 or more years for adults, but the Barrier’s effect was confounded with that of the drought. Nutrients, phytoplankton biomass, and a Microcystis abundance index showed little response to the Barrier. Transport of copepods — determined using output from a particle-tracking model — indicated some intermediate-scale reduction with the Barrier in place, but monitoring data did not show a larger-scale response in abundance. These studies were conducted separately and synthesized after the fact, and relied on reference conditions that were not always suitable for identifying the Barrier’s effects. If barriers are considered in the future, we rcommend a modest program of investigation to replicate study elements, and to ensure suitable reference conditions are available to allow barrier effects to be distinguished unambiguously from other sources of variability

Dye Tracing Through Thick Unsaturated Zones

Using the fluorescent dye Rhodamine WT, a field fluorometer, and direct samples of water collected from springs, wells, cave drips, and pools we have conducted two successful dye traces through thick unsaturated zones in karst regions. The first dye trace was of a proposed expansion site for a landfill in Winona County, southeastern Minnesota. The site sits on top of a narrow ridge about 150 meters above the adjacent valleys. The second trace was at Jewel Cave National Monument in the southern Black Hills of South Dakota. This trace was initiated to evaluate the impact of tourist facilities on the underlying cave. A visitor center was constructed on the surface, 50 to 100 meters directly above the cave. In both traces, small, irregular pulses of dye began to appear (in springs and wells at the Winona Landfill site and in cave drips and pools at Jewel Cave) within days of the dye injection, and the pulses continued to emerge for months. The pulses were typically a day or less in duration and a very small (10s to 100s of parts per trillion, 10- 12 g/g). The pulses are more frequent after major precipitation/runoff events but appear to be moving through both unsaturated zones in a very irregular, stochastic fashion. The very low levels of dye detected in many of the pulses required so.me type of confirmation analysis. We have successfully used the large negative temperature coefficient of Rhodamine WT's fluorescence to discriminate between low levels of Rhodamine WT and fluorescence due to background materials.Winona County and the Legislative Commission on Minnesota Resources. The dye trace of Jewel Cave was supported by a grant (USDI-CX-1200-5-A047) from the National Park Service

Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung

It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung

Abnormal lateralization of functional connectivity between language and default mode regions in autism

Background: Lateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders. Autism is characterized by a lack of left lateralization in structure and function of regions involved in language, such as Broca and Wernicke areas. Methods: Using functional connectivity magnetic resonance imaging from a large publicly available sample (n = 964), we tested whether abnormal functional lateralization in autism exists preferentially in language regions or in a more diffuse pattern across networks of lateralized brain regions. Results: The autism group exhibited significantly reduced left lateralization in a few connections involving language regions and regions from the default mode network, but results were not significant throughout left- and right-lateralized networks. There is a trend that suggests the lack of left lateralization in a connection involving Wernicke area and the posterior cingulate cortex associates with more severe autism. Conclusions: Abnormal language lateralization in autism may be due to abnormal language development rather than to a deficit in hemispheric specialization of the entire brain

Multisite functional connectivity MRI classification of autism: ABIDE results

Background:: Systematic differences in functional connectivity MRI metrics have been consistently observed in autism, with predominantly decreased cortico-cortical connectivity. Previous attempts at single subject classification in high-functioning autism using whole brain point-to-point functional connectivity have yielded about 80% accurate classification of autism vs. control subjects across a wide age range. We attempted to replicate the method and results using the Autism Brain Imaging Data Exchange (ABIDE) including resting state fMRI data obtained from 964 subjects and 16 separate international sites. Methods:: For each of 964 subjects, we obtained pairwise functional connectivity measurements from a lattice of 7266 regions of interest covering the gray matter (26.4 million “connections”) after preprocessing that included motion and slice timing correction, coregistration to an anatomic image, normalization to standard space, and voxelwise removal by regression of motion parameters, soft tissue, CSF, and white matter signals. Connections were grouped into multiple bins, and a leave-one-out classifier was evaluated on connections comprising each set of bins. Age, age-squared, gender, handedness, and site were included as covariates for the classifier. Results:: Classification accuracy significantly outperformed chance but was much lower for multisite prediction than for previous single site results. As high as 60% accuracy was obtained for whole brain classification, with the best accuracy from connections involving regions of the default mode network, parahippocampaland fusiform gyri, insula, Wernicke Area, and intraparietal sulcus. The classifier score was related to symptom severity, social function, daily living skills, and verbal IQ. Classification accuracy was significantly higher for sites with longer BOLD imaging times. Conclusions:: Multisite functional connectivity classification of autism outperformed chance using a simple leave-one-out classifier, but exhibited poorer accuracy than for single site results. Attempts to use multisite classifiers will likely require improved classification algorithms, longer BOLD imaging times, and standardized acquisition parameters for possible future clinical utility

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

Background: Hypertension is a complex condition and a common cardiovascular risk factor. Dietary docosahexaenoic acid (DHA) modulates atherosclerosis and hypertension, possibly via an inflammatory mechanism. IL‐1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL‐1 inhibition modulates blood pressure is unclear. Methods and Results: Male apoE−/− (apolipoprotein E–null) mice were fed either a high fat diet or a high fat diet plus DHA (300 mg/kg per day) for 12 weeks. Blood pressure and cardiac function were assessed, and effects of DHA on wall shear stress and atherosclerosis were determined. DHA supplementation improved left ventricular function, reduced wall shear stress and oscillatory shear at ostia in the descending aorta, and significantly lowered blood pressure compared with controls (119.5±7 versus 159.7±3 mm Hg, P<0.001, n=4 per group). Analysis of atheroma following DHA feeding in mice demonstrated a 4‐fold reduction in lesion burden in distal aortas and in brachiocephalic arteries (P<0.001, n=12 per group). In addition, DHA treatment selectively decreased plaque endothelial IL‐1β (P<0.01). Conclusions: Our findings revealed that raised blood pressure can be reduced by inhibiting IL‐1 indirectly by administration of DHA in the diet through a mechanism that involves a reduction in wall shear stress and local expression of the proinflammatory cytokine IL‐1β