The transcriptional profile of coronary arteritis in Kawasaki disease

BackgroundKawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.MethodsDeep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.ResultsT lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.ConclusionsThe immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies

Age of the Association between Helicobacter pylori and Man

When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya

Ancient DNA analysis suggests negligible impact of the Wari Empire expansion in Peru's Central Coast during the Middle Horizon

The analysis of ancient human DNA from South America allows the exploration of pre-Columbian population history through time and to directly test hypotheses about cultural and demographic evolution. The Middle Horizon (650-1100 AD) represents a major transitional period in the Central Andes, which is associated with the development and expansion of ancient Andean empires such as Wari and Tiwanaku. These empires facilitated a series of interregional interactions and socio-political changes, which likely played an important role in shaping the region's demographic and cultural profiles. We analyzed individuals from three successive pre-Columbian cultures present at the Huaca Pucllana archaeological site in Lima, Peru: Lima (Early Intermediate Period, 500-700 AD), Wari (Middle Horizon, 800-1000 AD) and Ychsma (Late Intermediate Period, 1000-1450 AD). We sequenced 34 complete mitochondrial genomes to investigate the potential genetic impact of the Wari Empire in the Central Coast of Peru. The results indicate that genetic diversity shifted only slightly through time, ruling out a complete population discontinuity or replacement driven by the Wari imperialist hegemony, at least in the region around present-day Lima. However, we caution that the very subtle genetic contribution of Wari imperialism at the particular Huaca Pucllana archaeological site might not be representative for the entire Wari territory in the Peruvian Central Coast.Guido Valverde, María Inés Barreto Romero, Isabel Flores Espinoza, Alan Cooper, Lars Fehren-Schmitz, Bastien Llamas, Wolfgang Haa

The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease

Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of potato shoots and generally results in unusable tubers. This disease has led to multi-million dollar losses for growers in the central and western United States over the past decade and impacts the livelihood of potato farmers in Mexico and New Zealand. ZC is associated with ‘Candidatus Liberibacter solanacearum’, a fastidious alpha-proteobacterium that is transmitted by a phloem-feeding psyllid vector, Bactericera cockerelli Sulc. Research on this disease has been hampered by a lack of robust culture methods and paucity of genome sequence information for ‘Ca. L. solanacearum’. Here we present the sequence of the 1.26 Mbp metagenome of ‘Ca. L. solanacearum’, based on DNA isolated from potato psyllids. The coding inventory of the ‘Ca. L. solanacearum’ genome was analyzed and compared to related Rhizobiaceae to better understand ‘Ca. L. solanacearum’ physiology and identify potential targets to develop improved treatment strategies. This analysis revealed a number of unique transporters and pathways, all potentially contributing to ZC pathogenesis. Some of these factors may have been acquired through horizontal gene transfer. Taxonomically, ‘Ca. L. solanacearum’ is related to ‘Ca. L. asiaticus’, a suspected causative agent of citrus huanglongbing, yet many genome rearrangements and several gene gains/losses are evident when comparing these two Liberibacter. species. Relative to ‘Ca. L. asiaticus’, ‘Ca. L. solanacearum’ probably has reduced capacity for nucleic acid modification, increased amino acid and vitamin biosynthesis functionalities, and gained a high-affinity iron transport system characteristic of several pathogenic microbes

Evaluation of binocular function among pre- and early-presbyopes with asthenopia

William Reindel,1 Lening Zhang,1 Joseph Chinn,2 Marjorie Rah1 1Vision Care, Bausch & Lomb Inc, Rochester, NY, 2J Chinn LLC, Lafayette, CO, USA Purpose: Individuals approaching presbyopia may exhibit ocular symptoms as they contend with visual demands of near work, coupled with natural age-related changes in accommodation. Therefore, accommodation and vergence of 30- to 40-year-old, myopic, soft contact lens wearing subjects with symptoms of asthenopia and no history of using multifocal lenses were evaluated.Patients and methods: In this prospective, observational study, 253 subjects with asthenopia were evaluated by 25 qualified practitioners, each at a different clinical site. Subjects were 30–40 years in age, had symptoms of soreness, eyestrain, tired eyes, or headaches with near work, regularly performed 2–3 consecutive hours of near work, and were undiagnosed with presbyopia. Amplitude of accommodation (AC) and near point convergence (NPC) were measured with a Royal Air Force binocular gauge. Triplicate push up and push down AC and NPC measures were recorded, and average AC values were compared to those calculated using the Hofstetter formula (HF). Results: The average AC push up/push down value was significantly better than the HF prediction for this age range (8.04±3.09 vs 6.23±0.80 D), although 22.5% of subjects had mean AC below their HF value (5.36±0.99 D). The average NPC push up/push down value was 12.0±4.69 cm. The mean binocular AC value using the push up measure was significantly better than the push down measure (8.5±3.4 vs 7.6±3.0 D). The mean NPC value using the push up measure was significantly worse than the push down measure (13.0±5.0 vs 11.0±4.7 cm). The most frequent primary diagnosis was ill-sustained accommodation (54%), followed by accommodative insufficiency (18%), and accommodative infacility (12%). Conclusion: Based upon a standardized assessment of accommodation and vergence, ill-sustained accommodation was the most frequent diagnosis among this population. Keywords: eyestrain, myopia, accommodation, vergence, lag, spherical aberration&nbsp

Evaluation of surface water characteristics of novel daily disposable contact lens materials, using refractive index shifts after wear

Jeffery Schafer,1 Robert Steffen,1 William Reindel,1 Joseph Chinn2 1Vision Care, Bausch & Lomb Incorporated, Rochester, NY, USA; 2J Chinn LLC, Lafayette, CO, USA Purpose: Contact lens wearers today spend much time using digital display devices. Contact lens manufacturers are challenged to develop products that account for longer periods of time where blink rate is reduced and tear-film evaporation rate is increased, affecting both visual acuity and comfort. Two manufacturers recently introduced novel daily disposable contact lenses with high surface water content. The objective of the present study was to compare surface water characteristics before and after initial wear of recently introduced nesofilcon A and delefilcon A high surface water lenses with those of etafilcon A lenses.Patients and methods: Twenty healthy subjects wore each of the three lens types studied in a randomly determined order for 15 minutes. After each wearing, lenses were removed and the surface refractive index (RI) of each lens was immediately measured.Results: The mean RI of the unworn delefilcon A lens was 1.34, consistent with water content in excess of 80%. After 15 minutes of wear, the surface RI shifted to 1.43, consistent with its reported 33% bulk water content. In contrast, the mean surface RI of the nesofilcon A lens was 1.38, both initially and after 15 minutes of wear, and that of the etafilcon A lens was 1.41 initially and 1.42 after 15 minutes of wear.Conclusion: The surface of the delefilcon A lens behaves like a high water hydrogel upon insertion but quickly dehydrates to behave like its low-water silicone-hydrogel bulk material with respect to surface water content during wear, while both nesofilcon A and etafilcon A lenses maintain their water content during initial wear. The nesofilcon A lens appears unique among high water lenses in maintaining high surface and bulk water content during wear. This is important because changes in surface RI due to dehydration are reported to lead to visual aberration affecting user experience.Keywords: contact lens dehydration, poloxamer, visual acuity, wettin