4,919 research outputs found
High Sequestration, Low Emission, Food Secure Farming. Organic Agriculture - a Guide to Climate Change & Food Security
- affordable high sequestration practices based on local resources
- enables continuous farmer-based adaptation to climate change
- ideal for the improvement of the world’s 400 million smallholder farms
- locally adapted, affordable and people centered
- empowers local communities
- established practices, systems and markets
- experience, practices and expertise to shar
Age-related changes of apoptotic cell death in human lymphocytes
Apoptosis seems to be involved in immunosenescence associated with aging. Moreover, in lymphocytes (PBL) of patients with Alzheimer's disease, an increased susceptibility to the apoptotic pathway has been described possibly due to impaired protection of oxidative stress. Accordingly, it seemed to be of particular interest to investigate the contribution of normal aging to the susceptibility from human lymphocytes to programmed cell death. We could show that PBL from elderly individuals (>60 years) accumulate apoptosing cells to a significant higher extent in spontaneous and activation-induced cell death compared to younger controls (<35 years). Treatment with the oxidative stressor 2-deoxy-D-ribose or with agonistic-CD95-antibody pronounced this effect even more implicating a higher sensitivity to reactive oxygen species and a higher functional CD95 expression, respectively. In addition, expression of the activation markers HLA-DR and CD95 was significantly increased in CD3+-cells of aged subjects, while expression of CD25 did not seem to be affected by age. Expression of Bcl-2 was increased in aging and correlated with the number of apoptotic cells
The central role of the transcriptional regulator IκBζ in psoriasis
IκBζ belongs to the group of atypical NF-κB inhibitors (IκBs). In contrast to classical
IκBs, IκBζ is only inducibly expressed in the cell nucleus, where it can inhibit, but more
importantly, also activate the expression of a particular subset of target genes.
NFKBIZ, the gene encoding IκBζ, has been identified as new risk gene in psoriasis.
Moreover, IκBζ knockout mice are protected in certain models of experimental
psoriasis. The aim of this thesis was to examine the global role of IκBζ in psoriasis in
order to find a new therapy approach. It could be shown that IκBζ is a regulator not
only of IL-17 but also of IL-36 signaling, which plays a major role in certain forms of
psoriasis. The IL-36-mediated induction of IκBζ was driven by NF-κB and STAT3, and
led to the expression of pro-inflammatory genes that initiate the development of
psoriasis. Accordingly, IκBζ knockout mice were completely protected from IL-36-
mediated experimental psoriasis. Thus, IκBζ represents a central regulator in psoriasis,
which promotes inflammation regardless of the type of stimulus. Based on this finding,
screenings for small-molecule inhibitors were performed that are able to repress the
induction of IκBζ. Thereby, I could identify a new pro-inflammatory signal pathway in
keratinocytes. In this pathway, CDK4/6 phosphorylated the methyltransferase EZH2,
which in turn methylated and activated STAT3, which transcriptionally induced IκBζ.
The pharmacological inhibition of CDK4/6 or EZH2 inhibited the pathogenesis of
psoriasis in vitro and in vivo.
In conclusion, this thesis not only validates IκBζ as an essential mediator of psoriasis,
but also identifies the CDK4/6-EZH2 axis as a novel mechanism whose inhibition could
provide a potential therapeutic option for the treatment of psoriasis
Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761)
Enhanced apoptosis and elevated levels of reactive oxygen species (ROS) play a major role in aging. In addition, several neurodegenerative diseases are associated with increased oxidative stress and apoptosis in neuronal tissue. Antioxidative treatment has neuro-protective effects. The aim of the present study was to evaluate changes of susceptibility to apoptotic cell death by oxidative stress in aging and its inhibition by the antioxidant Ginkgo biloba extract EGb761. We investigated basal and ROS-induced levels of apoptotic lymphocytes derived from the spleen in young (3 months) and old (24 months) mice. ROS were induced by 2-deoxy-D-ribose (dRib) that depletes the intracellular pool of reduced glutathione. Lymphocytes from aged mice accumulate apoptotic cells to a significantly higher extent under basal conditions compared to cells from young mice. Treatment with dRib enhanced this difference, implicating a higher sensitivity to ROS in aging. Apoptosis can be reduced in vitro by treatment with EGb761. In addition, mice were treated daily with 100mg/kg EGb761 per os over a period of two weeks. ROS-induced apoptosis was significantly reduced in the EGb761 group. Interestingly, this effect seemed to be more pronounced in old mice
Age-related impairment of human T lymphocytes' activation: specific differences between CD4+ and CD8+ subsets
The relevance of physiological immune aging is of great interest with respect to determining disorders with pathologic immune function in aging individuals. In recent years, the relevance of changes in peripheral lymphocytes in age-associated neurologic diseases has become more evident. Due to the lack of immunological studies, covering more than one event after mitogenic activation, we envisaged a new concept in the present study, aiming to investigate several events, starting from T cell receptor (TCR) ligation up to T cell proliferation. In addition, we addressed the question whether changes are present in the subsets (CD4, CD8) with aging. Phosphorylation of tyrosine residues declines with increasing age in CD4+ cells. Fewer levels of CD69 positive cells after 4 h mitogenic activation, altered expression of cytokines (IL2, IFN-gamma and TNF-alpha; 22 h) and lower proliferation (72 h) were determined in aging. Moreover, it could be shown that CD8+ lymphocytes react more effectively to mitogenic stimulation with reference to CD69 expression and proliferation in both age groups (60 years old). These data indicate that T cell activation, mediated by TCR engagement, is significantly impaired in aging and both subsets are affected. However, bypassing the TCR does not fully restore T cell function, indicating that there are more mechanisms involved than impaired signal transduction through TCR only. The results will be discussed in relation to their relevance in neurodegenerative and psychiatric disorders
A Weakly Nonlinear Analysis of Impulsively-Forced Faraday Waves
Parametrically-excited surface waves, forced by a periodic sequence of
delta-function impulses, are considered within the framework of the
Zhang-Vi\~nals model (J. Fluid Mech. 1997). The exact impulsive-forcing
results, in the linear and weakly nonlinear regimes, are compared with
numerical results for sinusoidal and multifrequency forcing. We find
surprisingly good agreement between impulsive forcing results and those
obtained using a two-term truncated Fourier series representation of the
impulsive forcing function. As noted previously by Bechhoefer and Johnson (Am.
J. Phys. 1996), in the case of two equally-spaced impulses per period there are
only subharmonic modes of instability. The familiar situation of alternating
subharmonic and harmonic resonance tongues emerges for unequally-spaced
impulses. We extend the linear analysis for two impulses per period to the
weakly nonlinear regime for one-dimensional waves. Specifically, we derive an
analytic expression for the cubic Landau coefficient in the bifurcation
equation as a function of the dimensionless fluid parameters and spacing
between the two impulses. As the capillary parameter is varied, one finds a
parameter region of wave amplitude suppression, which is due to a familiar 1:2
spatio-temporal resonance between the subharmonic mode of instability and a
damped harmonic mode. This resonance occurs for impulsive forcing even when
harmonic resonance tongues are absent from the neutral stability curve. The
strength of this resonance feature can be tuned by varying the spacing between
the impulses. This finding is interpreted in terms of a recent symmetry-based
analysis of multifrequency forced Faraday waves by Porter, Topaz and Silber
(Phys. Rev. Lett. 2004, Phys. Rev. E 2004).Comment: 13 pages, 10 figures, submitted to Physical Review
Grayanotoxin I Intoxication in Pet Pigs
Contaminated honey is a common cause of grayanotoxin intoxication in humans. Intoxication of animals, especially cattle, is usually due to ingestion of plants of the Ericaceae family, such as Rhododendron. Here, we report the ingestion of Pieris japonica as the cause of grayanotoxin I intoxication in 2 miniature pigs that were kept as pets. The pigs showed sudden onset of pale oral mucosa, tachycardia, tachypnea, hypersalivation, tremor, and ataxia that progressed to lateral recumbency. The pathological examination of one pig revealed no specific indications for intoxication except for the finding of plant material of Pieris japonica in the intestine. Grayanotoxin I was identified in the ingested plant, gastric content, blood, liver, bile, kidney, urine, lung, and skeletal muscle via HPLC-MS/MS. Grayanotoxin I should be considered as a differential etiological diagnosis in pigs with unspecific signs and discovery of ingested plant material as the only indication in the pathologic examination
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