The PlantsP and PlantsT Functional Genomics Databases.

PlantsP and PlantsT allow users to quickly gain a global understanding of plant phosphoproteins and plant membrane transporters, respectively, from evolutionary relationships to biochemical function as well as a deep understanding of the molecular biology of individual genes and their products. As one database with two functionally different web interfaces, PlantsP and PlantsT are curated plant-specific databases that combine sequence-derived information with experimental functional-genomics data. PlantsP focuses on proteins involved in the phosphorylation process (i.e., kinases and phosphatases), whereas PlantsT focuses on membrane transport proteins. Experimentally, PlantsP provides a resource for information on a collection of T-DNA insertion mutants (knockouts) in each kinase and phosphatase, primarily in Arabidopsis thaliana, and PlantsT uniquely combines experimental data regarding mineral composition (derived from inductively coupled plasma atomic emission spectroscopy) of mutant and wild-type strains. Both databases provide extensive information on motifs and domains, detailed information contributed by individual experts in their respective fields, and descriptive information drawn directly from the literature. The databases incorporate a unique user annotation and review feature aimed at acquiring expert annotation directly from the plant biology community. PlantsP is available at http://plantsp.sdsc.edu and PlantsT is available at http://plantst.sdsc.edu.

An Atlas of the Human Kinome Reveals the Mutational Landscape Underlying Dysregulated Phosphorylation Cascades in Cancer.

Kinase inhibitors are used widely to treat various cancers, but adaptive reprogramming of kinase cascades and activation of feedback loop mechanisms often contribute to therapeutic resistance. Determining comprehensive, accurate maps of kinase circuits may therefore help elucidate mechanisms of response and resistance to kinase inhibitor therapies. In this study, we identified and validated phosphorylatable target sites across human cell and tissue types to generate PhosphoAtlas, a map of 1,733 functionally interconnected proteins comprising the human phospho-reactome. A systematic curation approach was used to distill protein phosphorylation data cross-referenced from 38 public resources. We demonstrated how a catalog of 2,617 stringently verified heptameric peptide regions at the catalytic interface of kinases and substrates could expose mutations that recurrently perturb specific phospho-hubs. In silico mapping of 2,896 nonsynonymous tumor variants identified from thousands of tumor tissues also revealed that normal and aberrant catalytic interactions co-occur frequently, showing how tumors systematically hijack, as well as spare, particular subnetworks. Overall, our work provides an important new resource for interrogating the human tumor kinome to strategically identify therapeutically actionable kinase networks that drive tumorigenesis. Cancer Res; 76(7); 1733-45. ©2016 AACR.

Phorbol-12-myristate-13-acetate-treated human keratinocytes express B7-like molecules that serve a costimulatory role in T-cell activation.

In previous studies, Phorbol-12-myristate-13-acetate (PMA)-treated human keratinocytes (PMA-HNK) were shown to induce T-cell proliferation via a major histocompatibility complex (MHC)- and antigen (Ag)-independent mechanism, that was mediated in part by PMA-induced intercellular adhesion molecule (ICAM)-1 on HNK. Recently, the interaction of the B7 Ag on antigen-presenting cells with its ligand CD28 on T cells has been shown to deliver activation signals distinct from the interaction of MHC/Ag with the T-cell receptor. These findings led us to assess whether B7-dependent signals play a role in T-cell proliferation induced by PMA-HNK. We first examined B7 expression on HNK by staining with three different monoclonal antibodies (MoAbs). When analyzed by fluorescence-activated cell sorter, untreated HNK stained only faintly. By contrast, PMA induced a dose-dependent upregulation of B7 staining. This staining identifies a molecule closely related to B7 because it was blocked by purified recombinant B7 immunoglobulin. Upregulation of B7 staining was first observed 16 h after PMA treatment and persisted for at least 48 h; it was protein kinase C dependent and required de novo protein synthesis. Anti-B7 MoAbs reduced specifically the capacity of PMA-HNK to trigger proliferation of allogeneic peripheral blood mononuclear cells and T cells. The combination of anti-B7 and anti-ICAM-1 MoAbs further reduced this response. We conclude that PMA upregulates on HNK the expression of a B7-like molecule that contributes in concert with ICAM-1 to the capacity of PMA-HNK to induce proliferation of allogeneic T cells.

Development of a microarray assay that measures hybridization stoichiometry in moles.

Microarray data is most useful when it can be compared with other genetic detection technologies. In this report, we designed a microarray assay format that transforms raw data into a defined scientific unit (i.e., moles) by measuring the amount of array feature present and the cDNA sequence hybridized. This study profiles a mouse reference universal RNA sample on a microarray consisting of PCR products. In measuring array features, a labeled DNA sequence was designed that hybridizes to a conserved sequence that is present in every array feature. To measure the amount of cDNA sample hybridized, the RNA sample was processed to ensure consistent dye to DNA ratio for every labeled target cDNA molecule, using labeled branched dendrimers rather than by incorporation. A dye printing assay was then performed in order to correlate molecules of cyanine dye to signal intensity. We demonstrate that by using this microarray assay design, raw data can be transformed into defined scientific units, which will facilitate interpretation of other experiments, such as data deposited at the Gene Expression Omnibus and ArrayExpress.

[Diagnosis of eczema. Can you recognize what your patient's symptom?]. / Ekzemdiagnostik. Erkennen Sie, woran Ihr Patient leidet?

The term eczema is applied to specific non-infectious inflammatory reactions of the skin, and covers a number of etiologically highly heterogeneous conditions which, however, demonstrate common features in terms of clinical presentation and pathogenesis. Eczematous disorders account for approximately 20% of the dermatological disturbances. They include allergic, contact and irritant contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular-microbial and dyshidrotic eczema, and stasis eczema. They have a high individual and socio-economic impact, and are dependent on individual predisposition.

[Dermatological local therapy. How to control eczema]. / Dermatologische Lokaltherapie. Wie Sie Ekzemen auf die Pelle rücken.

The success of a topical treatment of eczema depends not only on the active agent employed, but also to a large extent on the choice of a suitable base. In the overview, therefore, not only the physical effects of the various galenic preparations (solution, shaking mixture, cream, etc.) are considered, but also the pharmacological and clinical effects of the topical corticoids and alternatives, such as, for example, bufexamac, dyes, coal tar, capsaicin, as also radiation treatment with UV-A in combination with psoralens.

[Occupational burden of the skin: the example of hands]. / Berufliche Belastung der Haut : Beispiel Hände.

The target body part primarily affected by stress in an occupation are the hands. The hands are involved in 90-95 % of the nearly 18,000 cases of occupation-related skin diseases registered every year. Harmful substances and stressing procedures, such as, e. g., wet work, tensides, organic solvents, lubricating coolants, metals, and even foods, are able to cause irritation of the skin. These noxious substances penetrate the skin and either cause direct damage of the protective skin barrier (irritative contact dermatitis (CD)) or provoke an immunological reaction (allergic CD); both will become manifest in eczemas of various forms. In order to avoid such eczemas preventive measures have to be taken. Primary prevention includes the reduction of harmful substances or even their replacement (e. g., chromate in cement or powder in latex gloves). Secondary prevention comprises, among other measures, training programs to educate in methods of skin protection and skin care. If all these measures are taken in a consistent manner the occurrence of skin diseases that are subject to compensation claims can be avoided.

[Topical corticosteroids versus topical inhibitors of calcineurin]. / Topische Kortikoide versus Calcineurinantagonisten.

Topical corticosteroids (TCC) have significantly shaped dermatological therapy for five decades. A few months ago the TCC were joined by competition, the topical inhibitors of calcineurin (TIC), wrongly termed topical immunomodulators. The present paper reviews the pharmacological effects and clinical efficacy of TIC, compares the risks, benefits and costs of those two groups of topical drugs and develops a position on the use of TIC. While TIC have ushered in a new era of topical anti-inflammatory therapy, the age of TCC is far from over.

Cytotoxicity and sensitization of povidone-iodine and other frequently used anti-infective agents.

Povidone-iodine is an antiseptic widely used in dermatology. In vitro experiments showed a certain cytotoxicity, yet it is not easy to transfer these toxicological data to in vivo circumstances. In vivo investigations in animals and in humans could exclude cytotoxic effects of povidone-iodine, measured by the wound healing process. Only when administered in combination with detergents was an obvious cytotoxicity seen in wounds but not on the intact skin. In comparison to the frequently used antibiotic neomycin, the sensitization rate of povidone-iodine is very low.

[Transdermal therapeutic systems (TTS)]. / Transdermale therapeutische Systeme (TTS).

The technique, pharmacokinetics, and advantages and disadvantages of transdermal drug delivery systems (TDS) are discussed. Special emphasis is laid on the dermatological problems arising during use of the TDS, such as irritation, sensitization, and the effects of occlusion, dermatoses, skin microflora and epidermal metabolism.

[Disorders of potency caused by sarcoidosis]. / Potenzstörungen durch Sarkoidose.

The case is reported of a dark-skinned African, whose hypophysis was altered by Boeck's disease, resulting in impairment of its function and in impotentia coeundi et generandi.

[Effect of zinc on wound healing]. / Der Einfluss von Zink auf die Wundheilung.

Topical application of zinc sulfate 0.5% leads to improvement of the healing process: In comparison to controls, the granulation tissue is constructed more systematically, the formation of collagen is more advanced, and its amount is increased.

[The nitrazine yellow test. A simple clinical method for diagnosing epidermal wound healing]. / Nitrazingelb-Test. Eine einfache klinische Methode zur Objektivierung der epidermalen Wundheilung.

Nitrazine yellow test has proved successful in determining toxic degenerative hand eczema. Additionally, it may be regarded as helpful in the quantitative registration of kinetic data on epidermal wound healing.

[Idiopathic progressive atrophoderma of Pasini-Pierini with the presence of antinuclear antibodies]. / Atrophodermia idiopathica progressiva Pasini-Pierini mit Vorkommen von antinukleären Antikörpern.

Atrophodermia idiopathica progressiva Pasini-Pierini (AIPP) in two young female patients is described. This disease, which begins in the second decade, is slowly progressive and has the characteristics of an originally atrophic dermatosis. No regression to sclerosised lesions could be observed. The distribution of lesions was a strictly one-sided, with the radicular pattern of some lesions suggesting the participation of neurogenic factors. The finding of antinuclear antibodies of the nucleolar type suggests an immunological pathogenesis. HLA typing did not reveal any extraordinary patterns or, interestingly, any of the types associated with immunological diseases.

[Does the anesthesia method modify the results of dermatologic surgery of the nose?]. / Beeinflusst das Anästhesieverfahren die Ergebnisse dermatochirurgischer Eingriffe an der Nase?

Since dermatosurgery has become a generally acknowledged subsection of dermatology, it seems strange that we have got so little account regarding the influences of anesthesia on the results of plastic surgery in the antrofacial region. A long-term follow-up of 139 patients, who had received regional flaps or free grafts because of tumors of the nose, revealed that the functional and esthetic results of operations carried out in local anesthesia were perfectly comparable with those in general anesthesia. We recommend local anesthesia because of its easy handling and little complications even in elderly polymorbid patients.