Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Mycoplasma pulmonis infection in rodents causes a chronic inflammatory airway disease with a strong immunological component, leading to mucosal remodeling and angiogenesis. We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. Changes in the shape of subepithelial OX6 (anti-MHC class II)-immunoreactive cells were evident in the tracheal mucosa 2 days after intranasal inoculation with M. pulmonis. By 1 week, the shape of the cells had changed from stellate to rounded (mean shape index increased from 0.42 to 0.77). The number of OX6-positive cells was increased 6-fold at 1 week and 16-fold at 4 weeks. Coincident with these changes, many columnar epithelial cells developed OX6 immunoreactivity, which was still present at 4 weeks. We conclude that M. pulmonis infection creates a potent immunologic stimulus that augments and transforms the OX6-immunoreactive cell population in the airways by changing the functional state of airway dendritic cells, initiating an influx of MHC class II expressing cells, and activating expression of MHC class II molecules by airway epithelial cells

Flexibility of Older Adults Aged 55–86 Years and the Influence of Physical Activity

Cross-sectional age-related differences in flexibility of older adults aged 55–86 years of varying activity levels were examined. Shoulder abduction and hip flexion flexibility measurements were obtained from 436 individuals (205 men, 71 ± 9 years; 231 women, 72 ± 8 years). Total physical activity was assessed using the Minnesota Leisure-Time Physical Activity Questionnaire. Shoulder abduction showed a significant decline averaging 5 degrees/decade in men and 6 degrees/decade in women. Piecewise linear regression showed an accelerated decline in men starting at the age of 71 years of 0.80 degrees/year, whereas in women the onset of decline (0.74 degrees/year) was 63 years. Men and women showed a significant decline in hip flexion (men: 6 degrees/decade; women: 7 degrees/decade). Piecewise linear regression revealed a rate of decline of 1.16 degrees/year beginning at 71 years in men and in women a single linear decline of 0.66 degrees/year. Multiple regression analysis showed that age and physical activity accounted for only 9% of the variance in hip flexion in women and 10% in men, with age but not physical activity remaining significant. Similarly for shoulder abduction, age was significant but not physical activity, in a model that described 8% of the variance for both sexes

Comparative Pathogenomics Reveals Horizontally Acquired Novel Virulence Genes in Fungi Infecting Cereal Hosts

Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens

A Search for Oxygen in the Low-Density Lyman-alpha Forest Using the Sloan Digital Sky Survey

We use 2167 Sloan Digital Sky Survey (SDSS) quasar spectra to search for low-density oxygen in the Intergalactic Medium (IGM). Oxygen absorption is detected on a pixel-by-pixel basis by its correlation with Lyman-alpha forest absorption. We have developed a novel Locally Calibrated Pixel (LCP) search method that uses adjacent regions of the spectrum to calibrate interlopers and spectral artifacts, which would otherwise limit the measurement of OVI absorption. Despite the challenges presented by searching for weak OVI within the Lyman-alpha forest in spectra of moderate resolution and signal-to-noise, we find a highly significant detection of absorption by oxygen at 2.7 < z < 3.2 (the null hypothesis has a chi^2=80 for 9 data points). We interpret our results using synthetic spectra generated from a lognormal density field assuming a mixed quasar-galaxy photoionizing background (Haardt & Madau 2001) and that it dominates the ionization fraction of detected OVI. The LCP search data can be fit by a constant metallicity model with [O/H] = -2.15_(-0.09)^(+0.07), but also by models in which low-density regions are unenriched and higher density regions have a higher metallicity. The density-dependent enrichment model by Aguirre et al. (2008) is also an acceptable fit. All our successful models have similar mass-weighted oxygen abundance, corresponding to [_MW] = -2.45+-0.06. This result can be used to find the cosmic oxygen density in the Lyman-alpha forest, Omega_(Oxy, IGM) = 1.4(+-0.2)x10^(-6) = 3x10^(-4) Omega_b. This is the tightest constraint on the mass-weighted mean oxygen abundance and the cosmic oxygen density in the Lyman-alpha forest to date and indicates that it contains approximately 16% of metals produced by star formation (Bouch\'e et al. 2008) up to z = 3.Comment: 12 pages, 9 figures. Accepted by ApJ (minor changes

Functionally specialized junctions between endothelial cells of lymphatic vessels

Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946–953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf–shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction–associated proteins, including occludin, claudin-5, zonula occludens–1, junctional adhesion molecule–A, and endothelial cell–selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule–1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics

Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation

Angiopoietin-2 (ANG2) regulates blood vessel remodeling in many pathological conditions through differential effects on Tie2 signaling. While ANG2 competes with ANG1 to inhibit Tie2, it can paradoxically also promote Tie2 phosphorylation (p-Tie2). A related paradox is that both inactivation and overactivation of Tie2 can result in vascular remodeling. Here, we reconciled these opposing actions of ANG2 by manipulating conditions that govern its actions in the vasculature. ANG2 drove vascular remodeling during Mycoplasma pulmonis infection by acting as a Tie2 antagonist, which led to p-Tie2 suppression, forkhead box O1 (FOXO1) activation, increased ANG2 expression, and vessel leakiness. These changes were exaggerated by anti-Tie2 antibody, inhibition of PI3K signaling, or ANG2 overexpression and were reduced by anti-ANG2 antibody or exogenous ANG1. In contrast, under pathogen-free conditions, ANG2 drove vascular remodeling by acting as an agonist, promoting high p-Tie2, low FOXO1 activation, and no leakage. Tie1 activation was strong under pathogen-free conditions, but infection or TNF-α led to Tie1 inactivation by ectodomain cleavage and promoted the Tie2 antagonist action of ANG2. Together, these data indicate that ANG2 activation of Tie2 supports stable enlargement of normal nonleaky vessels, but reduction of Tie1 in inflammation leads to ANG2 antagonism of Tie2 and initiates a positive feedback loop wherein FOXO1-driven ANG2 expression promotes vascular remodeling and leakage

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent

Arctic system on trajectory to new state

The Arctic system is moving toward a new state that falls outside the envelope of glacial-interglacial fluctuations that prevailed during recent Earth history. This future Arctic is likely to have dramatically less permanent ice than exists at present. At the present rate of change, a summer ice-free Arctic Ocean within a century is a real possibility, a state not witnessed for at least a million years. The change appears to be driven largely by feedback-enhanced global climate warming, and there seem to be few, if any processes or feedbacks within the Arctic system that are capable of altering the trajectory toward this “super interglacial” state

Extreme Longitudinal Variability of Plasma Structuring in the Equatorial Ionosphere on a Magnetically Quiet Equinoctial Day

We investigate the extreme longitudinal variability of equatorial scintillation under quiet magnetic conditions during 22–23 March 2002. Scintillation Network Decision Aid (SCINDA) observations show intense activity in the South American–Atlantic sector during local evening hours, whereas an absence of scintillation is seen in the far east Asian sector. Ground- and space-based measurements from SCINDA, the Global Ultraviolet Imager (GUVI), TOPEX, and a chain of GPS receivers are used in combination with the Utah State University Global Assimilation of Ionospheric Measurements (USU-GAIM) model to explore the relationship between the large-scale ionization distribution and small-scale irregularities at low latitudes in both the scintillating and nonscintillating longitude sectors. Our analysis shows that there are significant differences in the evolution of the ionization distributions during the evening hours, which are likely the result of differences in the daytime and postsunset vertical plasma drift in the two sectors. This study demonstrates the importance of USU-GAIM as a new tool for investigating longitudinal as well as day-to-day variability that is observed in the large-scale distribution of the ionosphere and how this relates to the occurrence of scintillation

Mass balance of nitrogen and phosphorus in an agricultural watershed : the shallow groundwater component

Partially funded by the Water Quality Strategic Research Initiative, Council on Food and Agricultural ResearchOpe