20 research outputs found
Search for lepton-flavor violation at HERA
A search for lepton-flavor-violating interactions and has been performed with the ZEUS detector using the entire HERA I
data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data
were taken at center-of-mass energies, , of 300 and 318 GeV. No
evidence of lepton-flavor violation was found, and constraints were derived on
leptoquarks (LQs) that could mediate such interactions. For LQ masses below
, limits were set on , where
is the coupling of the LQ to an electron and a
first-generation quark , and is the branching ratio of
the LQ to the final-state lepton ( or ) and a quark . For
LQ masses much larger than , limits were set on the four-fermion
interaction term for LQs that couple to an electron and a quark
and to a lepton and a quark , where and are
quark generation indices. Some of the limits are also applicable to
lepton-flavor-violating processes mediated by squarks in -Parity-violating
supersymmetric models. In some cases, especially when a higher-generation quark
is involved and for the process , the ZEUS limits are the most
stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig.
6) adde
Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s
Multijet production rates in neutral current deep inelastic scattering have
been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2.
The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s)
= 318 GeV using the ZEUS detector and correspond to an integrated luminosity of
82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster
algorithm in the longitudinally invariant inclusive mode. Measurements of
differential dijet and trijet cross sections are presented as functions of jet
transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with
E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD
calculations describe the data well. The value of the strong coupling constant
alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections,
is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.)
{+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure
New effects of caffeine on corticotropin-releasing hormone -induced stress along the intrafollicular classical hypothalamic-pituitary-adrenal and the neurogenic non-HPA axis in ex vivo human male androgenetic scalp hair follicles
Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuroendocrine equivalent of the systemic hypothalamic-pituitary-adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used corticotropin-releasing hormone (CRH), which triggers the HPA axis, to induce a stress response in human ex vivo male AGA HFs. Caffeine is known to reverse testosterone-mediated hair growth inhibition in the same hair organ culture model. To investigate whether caffeine would antagonize CRH-mediated stress in these HFs. HFs from balding vertex area scalp biopsies of men affected by AGA were incubated with CRH (10.sup.-7 mol L.sup.-1) with or without caffeine (0*001% or 0*005%). Compared to controls, CRH significantly enhanced the expression of catagen-inducing transforming growth factor-[beta]2 (TGF-[beta]2) (P < 0*001), CRH receptors 1 and 2 (CRH-R1/2) (P < 0*01), adrenocorticotropic hormone (ACTH) (P < 0*001) and melanocortin receptor 2 (MC-R2) (P < 0*001), and additional stress-associated parameters, substance P and p75 neurotrophin receptor (p75.sup.NTR). CRH inhibited matrix keratinocyte proliferation and expression of anagen-promoting insulin-like growth factor-1 (IGF-1) and the pro-proliferative nerve growth factor receptor NGF-tyrosine kinase receptor A (TrkA). Caffeine significantly counteracted all described stress effects and additionally enhanced inositol trisphosphate receptor (IP.sub.3-R), for the first time detected in human HFs. These findings provide the first evidence in ex vivo human AGA HFs that the stress mediator CRH induces not only a complex intrafollicular HPA response, but also a non-HPA-related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss, and that caffeine may effectively counteract stress-induced hair damage and possibly prevent stress-induced hair loss.Academi
Inhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces apoptosis in human melanoma cells
noProhormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy
Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine
Objectives
Although the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.
Methods
Human scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340â440 nm) + 20 mJ/cm2 UVB (290â320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organâcultured under serumâfree conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality readâout parameters were measured in defined skin and HF compartments.
Results
Consistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVRâmediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGFâ1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVRâmediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential upâregulation of the catagenâpromoting growth factor.
Conclusion
Our study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sunâprotective cosmeceutical and nutraceutical formulations.
We show here that solar UVA+UVB radiation impacting on the skin surface negatively affects HF functions, namely it triggers HF cytotoxicity, dystrophy, oxidative DNA damage, decrease in keratinocyte proliferation and increase in their apoptosis, stimulation of the production of transforming growth factor (TGF)âÎČ2 and decrease in insulin growth factor (IGF)â1 expression in ORS keratinocytes, premature catagen development, and perifollicular mast cell degranulation. UVâmediated damage is present throughout the HF length, but is more prominent in the upper layers of the skin (distal HF), as compared to the lower HF (central and proximal). Our study also shows that the topical application of 0.1% caffeine protects HFs from UVRâmediated damaged, namely it alleviated UVâmediated HF cytotoxicity and dystrophy, keratinocyte apoptosis in the distal and central ORS, and increased expression of TGFâÎČ2 in the proximal ORS.
Résumé
Objectifs
Alors que l'effet de rayons ultraviolets (RUV) sur la peau humaine a Ă©tĂ© largement Ă©tudiĂ©, on sait trĂšs peu de choses de l'impact des UV sur l'homĂ©ostasie du follicule pileux (FP). Ici, nous avons Ă©tudiĂ© l'effet du spectre des RUV solaires qui atteignent la surface de la peau humaine sur la biologie du FP, et si tout effet nocif peut ĂȘtre attĂ©nuĂ© par de la cafĂ©ine, un ingrĂ©dient cosmĂ©tique et neutraceutique largement utilisĂ©.
MĂthodes
Une peau de cuir chevelu humain avec ses FP terminaux a Ă©tĂ© irradiĂ©e ex vivo via lâĂ©piderme soit par 10 J/cm2 dâUVA (340â440 nm) + 20 mJ/cm2 dâUVB (290â320 nm) (dose faible) soit par 50 J/cm2 dâUVA + 50 mJ/cm2 dâUVB (dose Ă©levĂ©e) et placĂ©e en culture sans sĂ©rum pendant 1 ou 3 jours. 0,1% (5,15 mM) de cafĂ©ine a Ă©tĂ© appliquĂ©e par voie topique pendant 3 jours avant l'exposition aux UV Ă raison de 40 J/cm2 dâUVA + 40 mJ/cm2 UVB et pendant 3 jours aprĂšs l'exposition aux RUV. Les effets sur divers paramĂštres de toxicitĂ© et de vitalitĂ© ont Ă©tĂ© mesurĂ©s au niveau de compartiments dĂ©finis de la peau et des FP.
RĂsultats
CohĂ©rent avec les rĂ©sultats prĂ©cĂ©dents, les RUV transĂ©pidermique ont exercĂ© une cytotoxicitĂ© au niveau de la peau et des lĂ©sions Ă©pidermiques. Le traitement par des doses Ă©levĂ©es et/ou faibles dâUVA+UVB a Ă©galement induit des lĂ©sions oxydatives de lâADN et une cytotoxicitĂ© au niveau des FP humains. En outre, il a diminuĂ© la prolifĂ©ration et favorisĂ© l'apoptose de la gaine externe de la racine (ORS) du FP et des kĂ©ratinocytes de la matrice des cheveux (MC), a stimulĂ© le dĂ©veloppement de la phase catagĂšne, a rĂ©gulĂ© de maniĂšre diffĂ©rentielle l'expression des facteurs de croissance des FP, et induit une dĂ©granulation pĂ©rifolliculaire des mastocytes. Les lĂ©sions du FP mĂ©diĂ©es par les RUV Ă©taient plus graves aprĂšs une irradiation par dose Ă©levĂ©e de RUV et atteignaient Ă©galement les compartiments proximaux du FP. L'application topique de 0,1 % de cafĂ©ine n'a pas induit de cytotoxicitĂ© de la peau ou du FP et a stimulĂ© l'expression dâIGFâ1 dans la partie proximale de lâORS du FP. Cependant, elle a promu l'apoptose des kĂ©ratinocytes dans certains compartiments de FP. En outre, la cafĂ©ine a fourni une protection des FP contre la cytotoxicitĂ© et la dystrophie mĂ©diĂ©es par les RUV, l'apoptose des kĂ©ratinocytes et une rĂ©gulation Ă tendance positive de l'effet catagĂšne induit par le facteur de croissance.
Conclusion
Notre étude souligne la pertinence clinique de notre dosage d'irradiation UV ex vivo du cuir chevelu et fournit la premiÚre preuve que le rayonnement UV transépidermique affecte négativement d'importantes fonctions du FP chez l'homme. Cela suggÚre que l'intégration d'agents photoprotecteurs des FP tels que la caféine dans les formulations cosmétiques et nutraceutiques des écrans solaires pourrait constituer une stratégie prophylactique sensée