Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
Click here to view the accompanying paper in this issue. Videocasts of this article are available in: English: http://player.polyv.net/videos/player.swf?vid=f6ee5715d9808c7a481b7ae727da00dd_f Mandarin: http://player.polyv.net/videos/f6ee5715d98ae743a9b0509d0900c91f_f.swf
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
•The cooling performance of a multi-bed AMR device with gadolinium is presented.•A cooling power of 818 W with a COP of 4.2 was achieved over a 10 K span.•The device can establish a 16.6 K span ...starting from room temperature in 25 min.•Active valve control can increase cooling power and COP by more than 70%.•A maximum second-law efficiency of 39.2% was obtained at a span of 7.3 K.
We present the experimental results for a rotary magnetocaloric prototype that uses the concept of active magnetic regeneration, presenting an alternative to conventional vapor compression cooling systems. Thirteen packed-bed regenerators subjected to a rotating two-pole permanent magnet with a maximum magnetic field of 1.44 T are implemented. It is the first performance assessment of the prototype with gadolinium spheres as the magnetocaloric refrigerant and water mixed with commercial ethylene glycol as the heat transfer fluid. The importance of various operating parameters, such as fluid flow rate, cycle frequency, cold and hot reservoir temperatures, and blow fraction on the system performance is reported. The cycle frequency and utilization factor ranged from 0.5 to 1.7 Hz and 0.25 to 0.50, respectively. Operating near room temperature and employing 3.83 kg of gadolinium, the device produced cooling powers exceeding 800 W at a coefficient of performance of 4 or higher over a temperature span of above 10 K at 1.4 Hz. It was also shown that variations in the flow resistance between the beds could significantly limit the system performance, and a method to correct those is presented. The performance metrics presented here compare well with those of currently existing magnetocaloric devices. Such a prototype could achieve efficiencies as high as conventional vapor compression systems without the use of refrigerants that have high global warming potential.
CNT/crystalline Fe nanocomposites (see Figure) have excellent microwave‐absorption characteristics. This absorption property is shown to result from the confinement of crystalline Fe in carbon ...nanoshells, deriving mainly from magnetic rather than electric effects—the complex permittivity and permeability depend both on the shape and phase of the CNT/Fe nanocapsulates.
Finite range ferromagnetism and antiferromagnetism in two-dimensional (2D) systems within an isotropic Heisenberg model at non-zero temperature were originally proposed to be impossible. However, ...recent theoretical studies using an Ising model have shown that 2D magnetic crystals can exhibit magnetism. Experimental verification of existing 2D magnetic crystals in this system has remained exploratory. In this work we exfoliated CrSiTe3, a bulk ferromagnetic semiconductor, to mono- and few-layer 2D crystals onto a Si/SiO2 substrate. Raman spectra indicate good stability and high quality of the exfoliated flakes, consistent with the computed phonon spectra of 2D CrSiTe3, giving strong evidence for the existence of 2D CrSiTe3 crystals. When the thickness of the CrSiTe3 crystals is reduced to a few layers, we observed a clear change in resistivity at 80-120 K, consistent with theoretical calculations of the Curie temperature (Tc) of similar to 80 K for the magnetic ordering of 2D CrSiTe3 crystals. The ferromagnetic mono- and few-layer 2D CrSiTe3 indicated here should enable numerous applications in nano-spintronics.
Identification of all expressed transcripts in a sequenced genome is essential both for genome analysis and for realization of the goals of systems biology. We used the transcriptional profiling ...technology called 'massively parallel signature sequencing' to develop a comprehensive expression atlas of rice (Oryza sativa cv Nipponbare). We sequenced 46,971,553 mRNA transcripts from 22 libraries, and 2,953,855 small RNAs from 3 libraries. The data demonstrate widespread transcription throughout the genome, including sense expression of at least 25,500 annotated genes and antisense expression of nearly 9,000 annotated genes. An additional set of ∼15,000 mRNA signatures mapped to unannotated genomic regions. The majority of the small RNA data represented lower abundance short interfering RNAs that match repetitive sequences, intergenic regions and genes. Among these, numerous clusters of highly regulated small RNAs were readily observed. We developed a genome browser (http://mpss.udel.edu/rice) for public access to the transcriptional profiling data for this important crop.
The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No ...study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH.
We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (
monotherapy
combination therapy).
There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53).
There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.
The Red River is one of the largest contributing sources
of discharge and nutrients to the world's 10th largest freshwater lake,
Lake Winnipeg. Conversion of large areas of annual cropland to
...perennial forage has been proposed as a strategy to reduce both flooding
and nutrient export to Lake Winnipeg. Such reductions could occur either via a reduction in the concentration of nutrients in runoff or through changes in
the basin-scale hydrology, resulting in a lower water yield and the concomitant
export of nutrients. This study assessed the latter mechanism by using the
physically based Cold Regions Hydrological Modelling platform to examine the
hydrological impacts of land use conversion from annual crops to perennial
forage in a subbasin of the La Salle River basin in Canada. This basin is a typical
agricultural subbasin in the Red River Valley, characterised by flat
topography, clay soils, and a cold subhumid, continental climate. Long-term
simulations (1992–2013) of the major components of water balance were
compared between canola and smooth bromegrass, representing a conversion
from annual cropping systems to perennial forage. An uncertainty framework
was used to represent a range of fall soil saturation status (0 % to 70 %),
which governs the infiltration to frozen soil in the subsequent spring. The model
simulations indicated that, on average, there was a 36.5 ± 6.6 %
(36.5 ± 7.2 mm) reduction in annual cumulative discharge and a
29.9 ± 16.3 % (2.6 ± 1.6 m3 s−1) reduction in annual
peak discharge due to forage conversion over the assessed period. These
reductions were driven by reduced overland flow 52.9 ± 12.8 %
(28.8 ± 10.1 mm), increased peak snowpack (8.1 ± 1.5 %,
7.8 ± 1.6 mm), and enhanced infiltration to frozen soils (66.7 ± 7.7 %, 141.5 ± 15.2 mm). Higher cumulative evapotranspiration (ET)
from perennial forage (34.5 ± 0.9 %, 94.1 ± 2.5 mm) was also
predicted by the simulations. Overall, daily soil moisture under perennial
forage was 18.0 % (57.2 ± 1.2 mm) higher than that of crop simulation,
likely due to the higher snow water equivalent (SWE) and enhanced
infiltration. However, the impact of forage conversion on daily soil
moisture varied interannually. Soil moisture under perennial forage stands
could be either higher or lower than that of annual crops, depending on
antecedent spring snowmelt infiltration volumes.
Loss of HOXA5 expression occurs frequently in breast cancer and correlates with higher pathological grade and poorer disease outcome. However, how HOX proteins drive differentiation in mammalian ...cells is poorly understood. In this paper, we investigated cellular and molecular consequences of loss of HOXA5 in breast cancer, and the role played by retinoic acid in HOXA5 function. Analysis of global gene expression data from HOXA5-depleted MCF10A breast epithelial cells, followed by validation, pointed to a role for HOXA5 in maintaining several molecular traits typical of the epithelial lineage such as cell-cell adhesion, tight junctions and markers of differentiation. Depleting HOXA5 in immortalized MCF10A or transformed MCF10A-Kras cells reduced their CD24
/CD44
population, enhanced self-renewal capacity and reduced expression of E-cadherin (CDH1) and CD24. In the case of MCF10A-Kras, HOXA5 loss increased branching and protrusive morphology in Matrigel, all features suggestive of epithelial to basal transition. Further, orthotopically implanted xenografts of MCF10A-Kras-scr grew as well-differentiated pseudo-luminal carcinomas, while MCF10A-Kras-shHOXA5 cells formed aggressive, poorly differentiated carcinomas. Conversely, ectopic expression of HOXA5 in aggressive SUM149 or SUM159 breast cancer cells reversed the cellular and molecular alterations observed in the HOXA5-depleted cells. Retinoic acid is a known upstream regulator of HOXA5 expression. HOXA5 depletion in MCF10A cells engineered to express doxycycline-induced shHOXA5 slowed transition of cells from a less differentiated CD24
/CD44
to the more differentiated CD24
/CD44
state. This transition was promoted by retinal treatment, which upregulated endogenous HOXA5 expression and caused re-expression of occludin and claudin-7 (CLDN7). Expression of CDH1 and CD24 was transcriptionally upregulated by direct binding of HOXA5 to their promoter sequences as demonstrated by luciferase and ChIP analyses. Thus, loss of HOXA5 in mammary cells leads to loss of epithelial traits, an increase in stemness and cell plasticity, and the acquisition of more aggressive phenotypes.
Interactions between rice and Magnaporthe oryzae involve the recognition of cellular components and the exchange of complex molecular signals from both partners. How these interactions occur in rice ...cells is still elusive. We employed robust-long serial analysis of gene expression, massively parallel signature sequencing, and sequencing by synthesis to examine transcriptome profiles of infected rice leaves. A total of 6,413 in planta-expressed fungal genes, including 851 genes encoding predicted effector proteins, were identified. We used a protoplast transient expression system to assess 42 of the predicted effector proteins for the ability to induce plant cell death. Ectopic expression assays identified five novel effectors that induced host cell death only when they contained the signal peptide for secretion to the extracellular space. Four of them induced cell death in Nicotiana benthamiana. Although the five effectors are highly diverse in their sequences, the physiological basis of cell death induced by each was similar. This study demonstrates that our integrative genomic approach is effective for the identification of in planta-expressed cell death-inducing effectors from M. oryzae that may play an important role facilitating colonization and fungal growth during infection.
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