101,900 research outputs found
Assessing Phosphorylation of STAT Transcription Factors in Mouse Innate Lymphoid Cells
No full textInnate lymphoid cells (ILCs) ensure protection against pathogens by quickly reacting to the alterations of the cytokine milieu taking place upon infection. More than 50 cytokines and growth factors activate the Janus kinases (JAKs), leading to phosphorylation of members of the signal transducer and activator of transcription (STAT) family. Activation of STATs induces specific transcriptional programs which are associated with distinct cellular outcomes. Thus, an efficient measurement of rapid STAT phosphorylation enables not only to dissect the spectrum of cytokine sensitivity among ILC subsets but also to pinpoint specific transcriptional programs and cellular functions initiated after activation. Using this method, we have previously dissected the downstream events of Interleukin (IL)-23 and IL-12 signaling in ILCs, shedding light on the differential usage of STATs among ILC subsets. Here, we provide an optimized and detailed protocol describing how to analyze phosphorylation of STAT transcription factors in murine NK and ILC subsets isolated from different tissues
NK cell and ILC heterogeneity in colorectal cancer. New perspectives from high dimensional data
No full textInnate lymphoid cells (ILCs) and tissue-resident natural killer (NK) cells ensure immunity at environmental interfaces and help maintain barrier integrity of the intestinal tract. This wide range of innate lymphocytes is able to provide fast and potent inflammatory responses that, when deregulated, have been associated with pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the presence of tumor-infiltrating NK cells is generally associated with a favorable outcome in CRC patients, emerging evidence reveals distinct roles for ILCs in regulating CRC pathogenesis and progression. Advances in next generation sequencing technology, and in particular of single-cell RNA-seq approaches, along with multidimensional flow cytometry analysis, have helped to deconvolute the complexity and heterogeneity of the ILC system both in homeostatic and pathological contexts. In this review, we discuss the protective and detrimental roles of NK cells and ILCs in the pathogenesis of CRC, focusing on the phenotypic and transcriptional modifications these cells undergo during CRC development and progression
MAL daylight photodynamic therapy for actinic keratosis: Clinical and imaging evaluation by 3D camera
No full textNon-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild-moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex© camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1-3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL-PDT’s increasing compliance
Smyd3 open & closed lock mechanism for substrate recruitment: The hinge motion of C-terminal domain inferred from μ-second molecular dynamics simulations
No full textBACKGROUND:
The human lysine methyltransferase Smyd3, a member of the SET and MYND domain containing protein family, harbors methylation activity on both histone and non-histone targets in a tightly regulated manner. The mechanism of how Smyd3 dynamically regulates substrate recognition is still not fully unveiled.
METHODS:
Here, we employed molecular dynamics simulations on full length human Smyd3, performed to a total of 1.2 μ-second, in the presence (holo) and absence (apo) of the S-Adenosyl methionine (AdoMet) cofactor. The dynamical features of Smyd3 in apo and holo states have been examined and compared via examining geometrical and electrostatic properties.
RESULTS:
The results show a distinct dynamics of the C-terminal domain (CTD) in the two states. In the apo state, the CTD undergoes a large hinge like motion and samples more opened configurations, thus acting like a loosened clamp and resulting in expanded substrate binding crevice. In the holo state, the CTD exhibits a restricted motion while the overall structure remains compact, mimicking a closed clamp. This leads to a localized increase in the negative potential at the substrate binding cleft. Further, solvent accessibility of critical residues at the target lysine access channel, important for methylation activity, is increased.
CONCLUSIONS:
We postulate that AdoMet cofactor acts like a key and locks Smyd3 in a closed conformation. In effect, the cofactor binding restricts the elasticity of the CTD, presenting a compact substrate binding cleft with high negative potential, which may have implications on substrate recruitment via long range electrostatics.
GENERAL SIGNIFICANCE:
The deletion of the CTD from Smyd3 has been shown to abolish the basal histone methylation activity. Our study highlights the importance of the CTD elasticity in shaping the substrate binding site for recognition and supports the previously proposed role of the CTD in stabilizing the active site for methylation activity
Arterial hypertension and cardiovascular risk: need for a combined strategy of intervention
No full textArterial hypertension represents one of the most common conditions associated with an increased cardiovascular risk. New evidences support the need to adopt a global approach to the treatment of cardiovascular risk in hypertensive subjects by using drugs with proven benefits, not only for blood pressure control, but also for their pleiotropic effects. A greater understanding of the pathogenetic mechanisms of hypertension would provide a better strategy for preventing and treating this condition. Angiotensin II seems to be responsible for triggering vascular inflammation by inducing oxidative stress, resulting in up-regulation of pro-inflammatory mediators that lead to endothelial dysfunction and vascular injury. The interaction of angiotensin II, oxidative stress and endothelial dysfunction might be a target of a new integrated approach with important clinical implications
[Arterial hypertension and cardiovascular risk: need for a combined strategy of intervention].
No full textWISE Workshops : Foundations for Collaborative Cyber Security Learning: Exploring Educator and Learner Requirements ; Reimaging Inclusive Pedagogy in Cybersecurity Education (A Workshop Proposal)
No full textBackmatter - WISE Workshop.Foundations for Collaborative Cyber Security Learning: Exploring Educator and Learner Requirements, Jerry Andriessen, Steven Furnell, Gregor Langner, Gerald Quirchmayr, Vittorio Scarno, Teemu Tokola.Reimaging Inclusive Pedagogy in Cybersecurity Education (A Workshop Proposal), Angela G. Jackson-Summers.International audienceThis brief paper outlines the background to a workshop session at the 14th World Conference on Information Security Education (WISE 14), drawing upon early findings from the Collaborative Cybersecurity Awareness Learning (COLTRANE) project funded under the European Union ERASMUS + programme. It presents the background to the COLTRANE project and an outline of the workshop focus. The latter is based upon an investigation of current cyber security education delivery that has been conducted amongst existing educators and learners via prior survey-based data collection and follow-up workshop discussions within individual COLTRANE partner countries
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Subclinical atherosclerosis in systemic sclerosis: Different risk profiles among patients according to clinical manifestations
No full textIntroduction: Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways. Aim: To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients. Methods: Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods: carotid ultrasound and flow mediated dilation (FMD) of the brachial artery. Results: Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P =.006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8 mm vs 0.55 mm; P <.0001) while FMD was significantly lower (median value 9% vs 14%; P =.0086) in patients compared to healthy controls. Among the SSc patients, thickening of CCA-IMT was significantly associated with the presence of diastolic dysfunction of left ventricle (absence of diastolic dysfunction: odds ratio [OR] 0.2, 95% CI 0.04-0.92, P =.038) and with a higher Framingham score (OR 1.3, 95% CI 1.03-1.6], P =.024). The diffuse cutaneous form was slightly protective against pathological FMD (OR 0.12, 95% CI 0.022-0.71, P =.019). Conclusions: This study confirms the involvement of macrocirculation in SSc patients, detecting the presence of subclinical ATS markers more frequently in patients compared to healthy controls. Framingham score, diastolic dysfunction of left ventricle and limited cutaneous form of the disease appeared to be associated with a higher risk of developing ATS
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