Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to ...colorectal cancer is not well understood.
To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate DSS, 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APCfl/fl murine models of colitis-associated cancer.
DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11b+F4/80+Ly6Chigh macrophages and CD11b+Ly6G+ neutrophils. Interestingly, depletion of the CD11b+F4/80+Ly6Chigh macrophages inhibited tumorigenesis, whereas depletion of CD11b+Ly6G+ neutrophils had no effect on tumorigenesis. Furthermore, the macrophage-derived cytokines interleukin-1β, tumor necrosis factor–α, and interleukin-6 were significantly increased in DSS colitis and promoted stemness of Dclk1+ tuft cells that serve as the cellular origin of cancer.
We have identified CD11b+F4/80+Ly6Chigh macrophages as key mediators of cancer initiation in colitis-associated cancer. Development of new therapies that target these cells may provide an effective preventative strategy for colitis-associated cancer.
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Proliferative control in cancer cells is frequently disrupted by mutations in the retinoblastoma protein (RB) pathway. Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells ...whose RB pathway is already compromised by another mutation. In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. We generated isogenic RB1 mutant genotypes with CRISPR/Cas9 in a number of cell lines. Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. When xenografted into immunocompromised mice, RB1 mutant cells exhibit an elevated propensity to seed new tumors in recipient lungs. This study offers evidence that late-arising RB1 mutations can facilitate genome instability and cancer progression that are beyond the preexisting proliferative control deficit.
Scleractinian corals are engineers on coral reefs that provide both structural complexity as habitat and sustenance for other reef-associated organisms via the release of organic and inorganic ...matter. However, coral reefs are facing multiple pressures from climate change and other stressors, which can result in mass coral bleaching and mortality events. Mass mortality of corals results in enhanced release of organic matter, which can cause significant alterations to reef biochemical and recycling processes. There is little known about how long these nutrients are retained within the system, for instance, within the tissues of other benthic organisms. We investigated changes in nitrogen isotopic signatures (δ
15
N) of macroalgal tissues (a) ~ 1 year after a bleaching event in the Seychelles and (b) ~ 3 months after the peak of a bleaching event in Mo’orea, French Polynesia. In the Seychelles, there was a strong association between absolute loss in both total coral cover and branching coral cover and absolute increase in macroalgal δ
15
N between 2014 and 2017 (adjusted
r
2
= 0.79,
p
= 0.004 and adjusted
r
2
= 0.86,
p
= 0.002, respectively). In Mo’orea, a short-term transplant experiment found a significant increase in δ
15
N in
Sargassum mangarevense
after specimens were deployed on a reef with high coral mortality for ~ 3 weeks (
p
< 0.05). We suggest that coral-derived nutrients can be retained within reef nutrient cycles, and that this can affect other reef-associated organisms over both short- and long-term periods, especially opportunistic species such as macroalgae. These species could therefore proliferate on reefs that have experienced mass mortality events, because they have been provided with both space and nutrient subsidies by the death and decay of corals.
What Next for Agriculture After Durban? Beddington, J. R.; Asaduzzaman, M.; Clark, M. E. ...
Science (American Association for the Advancement of Science),
01/2012, Letnik:
335, Številka:
6066
Journal Article
Recenzirano
Despite obstacles in the UN climate talks, modest progress and opportunities for scientific input on agriculture arose.
Global agriculture must produce more food to feed a growing population. Yet ...scientific assessments point to climate change as a growing threat to agricultural yields and food security (
1
–
4
). Recent droughts and floods in the Horn of Africa, Russia, Pakistan, and Australia affected food production and prices. The Intergovernmental Panel on Climate Change predicts that the frequency of such extreme weather events will increase (
5
), which, when combined with poverty, weak governance, conflict, and poor market access, can result in hunger and famine. At the same time, agriculture exacerbates climate change when greenhouse gases (GHGs) are released by land clearing, inappropriate fertilizer use, and other practices (
6
).
Blackleg disease of canola in Australia Van De Wouw, A. P; S. J. Marcroft; B. J. Howlett
Crop and pasture science,
01/2016, Letnik:
67, Številka:
4
Journal Article
Recenzirano
Blackleg disease caused by the fungus Leptosphaeria maculans is the most important disease of canola worldwide. The impact of this disease on the development of the Australian canola industry, ...particularly over the last 20 years, is discussed. Deployment of a range of disease control measures has resulted in a thriving canola industry with production now approaching 4million tonnes annually. Discoveries about disease mechanisms and key plant and fungal genes are described. Analysis of the L. maculans genome sequence has enabled an understanding of how fungal populations can evolve rapidly to overcome disease resistance bred into canola cultivars.
Leptosphaeria maculans 'brassicae' is a damaging fungal pathogen of canola (Brassica napus), causing lesions on cotyledons and leaves, and cankers on the lower stem. A related species, L. biglobosa ...'canadensis', colonises cotyledons but causes few stem cankers. We describe the complement of genes encoding carbohydrate-active enzymes (CAZys) and peptidases of these fungi, as well as of four related plant pathogens. We also report dual-organism RNA-seq transcriptomes of these two Leptosphaeria species and B. napus during disease. During the first seven days of infection L. biglobosa 'canadensis', a necrotroph, expressed more cell wall degrading genes than L. maculans 'brassicae', a hemi-biotroph. L. maculans 'brassicae' expressed many genes in the Carbohydrate Binding Module class of CAZy, particularly CBM50 genes, with potential roles in the evasion of basal innate immunity in the host plant. At this time, three avirulence genes were amongst the top 20 most highly upregulated L. maculans 'brassicae' genes in planta. The two fungi had a similar number of peptidase genes, and trypsin was transcribed at high levels by both fungi early in infection. L. biglobosa 'canadensis' infection activated the jasmonic acid and salicylic acid defence pathways in B. napus, consistent with defence against necrotrophs. L. maculans 'brassicae' triggered a high level of expression of isochorismate synthase 1, a reporter for salicylic acid signalling. L. biglobosa 'canadensis' infection triggered coordinated shutdown of photosynthesis genes, and a concomitant increase in transcription of cell wall remodelling genes of the host plant. Expression of particular classes of CAZy genes and the triggering of host defence and particular metabolic pathways are consistent with the necrotrophic lifestyle of L. biglobosa 'canadensis', and the hemibiotrophic life style of L. maculans 'brassicae'.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many plant-pathogenic fungi have a tendency towards genome size expansion, mostly driven by increasing content of transposable elements (TEs). Through comparative and evolutionary genomics, five ...members of the Leptosphaeria maculans-Leptosphaeria biglobosa species complex (class Dothideomycetes, order Pleosporales), having different host ranges and pathogenic abilities towards cruciferous plants, were studied to infer the role of TEs on genome shaping, speciation, and on the rise of better adapted pathogens.
L. maculans 'brassicae', the most damaging species on oilseed rape, is the only member of the species complex to have a TE-invaded genome (32.5%) compared to the other members genomes (<4%). These TEs had an impact at the structural level by creating large TE-rich regions and are suspected to have been instrumental in chromosomal rearrangements possibly leading to speciation. TEs, associated with species-specific genes involved in disease process, also possibly had an incidence on evolution of pathogenicity by promoting translocations of effector genes to highly dynamic regions and thus tuning the regulation of effector gene expression in planta.
Invasion of L. maculans 'brassicae' genome by TEs followed by bursts of TE activity allowed this species to evolve and to better adapt to its host, making this genome species a peculiarity within its own species complex as well as in the Pleosporales lineage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
...basal innate immunity, a mechanism common to animals and plants, is not triggered. Furthermore, there is generally no intimate cellular relationship between fungus and animal as exists for ...obligate biotrophs or symbionts, which are enveloped in fungal and plant plasmalemmas. ...effectors may not be necessary to mediate deceit in all fungal-animal interactions, but are likely to be crucial for interactions that deceitful and affectionate fungi have with plants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The burden of neurological disorders is large and altered by the HIV epidemic.
We describe the pattern of neurological disorders and their association with HIV infection in adult patients attending a ...consultant hospital in Northern Tanzania.
In this prospective cross-sectional study, we collected data on adult neurological referrals over a 6-year period between 2007-13. The odds of HIV infection, across neurological categories adjusted for age and sex, was calculated.
Of 2037 participants, 54.8% were male and 45.2% were female. The median age of participants was 43 years. The results for HIV screening were available for 992/2037 (48.7%) patients, of whom 306 (30.8%) were seropositive. The most frequent neurological disorders were cerebrovascular disease (19.9%), paraplegia (13.6%), and peripheral neuropathies (8%). Taken together CNS infection accounted for 278/2037 (13.6%). The adjusted odds (aOR) of HIV infection was highest amongst infections; brain abscesses (aOR 107, 95% CI 35.1-470.4) and meningitis/encephalitis (aOR 40.1, 95% CI 13.6-172.9), but also raised in cerebrovascular disease, paraplegia, peripheral neuropathies, cranial nerve palsies, seizures, cerebllar disorders, movement disorders, motor neuron disease and headache.
The main pattern of neurological disorders in Northern Tanzania is presented. The odds of HIV infection was highest in CNS infections and in a wide range of non-communicable neurological disorders.
In a clinical setting, pain is reported either through patient self-report or via an observer. Such measures are problematic as they are: 1) subjective, and 2) give no specific timing information. ...Coding pain as a series of facial action units (AUs) can avoid these issues as it can be used to gain an objective measure of pain on a frame-by-frame basis. Using video data from patients with shoulder injuries, in this paper, we describe an active appearance model (AAM)-based system that can automatically detect the frames in video in which a patient is in pain. This pain data set highlights the many challenges associated with spontaneous emotion detection, particularly that of expression and head movement due to the patient's reaction to pain. In this paper, we show that the AAM can deal with these movements and can achieve significant improvements in both the AU and pain detection performance compared to the current-state-of-the-art approaches which utilize similarity-normalized appearance features only.
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