The role of the conversion of IBA into IAA on root regeneration in apple: introduction of a test system

A test system for root regeneration was developed that consists of stem slices of apple shoots (ca. 0.5 mm thick; fresh weight ca. 1 mg). Roots regenerated synchronously without intervening callus formation and without interference with compounds originating from other parts of the plant. Supply of indolebutyric acid (IBA) or indoleacetic acid (IAA) induced maximally an average of 8 or 4.5 roots per slice, respectively. After uptake of IBA, a high degree of conjugation resulted in a recovery of 2.5% as internal free IBA (ca. 2 times the medium concentration). Due to conversion of absorbed IBA into IAA a fraction of 0.4% was recovered as (physiologically active) free IAA. After incubation on medium with IAA, 0.5% of the absorbed hormone was recovered in the free acid form. No conversion of IAA into IBA was observed. Equimolar contents of internal free IAA after incubation on IBA or IAA resulted for IBA in a higher number of roots than for IAA. This means that IBA may also act via internal free IBA or may synergistically modify the action or endogenous synthesis of IAA.Abbreviations BHT butyl hydroxy toluene - EtOH ethanol - FW fresh weight - HAc acetic acid - HPLC high performance liquid chromatography - IAA indoleacetic acid - IAA^int free (internal) IAA in the tissue derived from IBA or IAA uptake - IBA indolebutyric acid - IBA^int free (internal) IBA in the tissue derived from IBA or IAA uptake - MeOH methanol - PAR photosynthetic active radiation - SEM standard error of the mean - TLC thin layer chromatography - UV ultra violet     

An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56^dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children.     

Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature

Metformin is one of the most prescribed drugs in the world giving potential health benefits beyond that of type 2 diabetes (T2DM). Emerging evidence suggests that it may have protective effects for retinal/posterior segment diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD), inherited retinal degeneration such as retinitis pigmentosa (RP), primary open angle glaucoma (POAG), retinal vein occlusion (RVO), and uveitis. Metformin exerts potent anti-inflammatory, antiangiogenic, and antioxidative effects on the retina in response to pathologic stressors. In this review, we highlight the broad mechanism of action of metformin through key preclinical studies on animal models and cell lines used to simulate human retinal disease. We then explore the sparse but promising retrospective clinical data on metformin’s potential protective role in DR, AMD, POAG, and uveitis. Prospective clinical data is needed to clarify metformin’s role in management of posterior segment disorders. However, given metformin’s proven broad biochemical effects, favorable safety profile, relatively low cost, and promising data to date, it may represent a new therapeutic preventive and strategy for retinal diseases.     

Epigenetic chromatin modifiers in barley: III. Isolation and characterization of the barley GNAT-MYST family of histone acetyltransferases and responses to exogenous ABA

Histone acetylation is a vital mechanism for the activation of chromatin and the corresponding expression of genes competing the action of histone deacetylation and leading to chromatin inactivation. Histone acetyltransferases (HATs) comprise a superfamily including the GNAT/MYST, CBP and TF_II250 families. Histone acetyltransferases have been well studied in Arabidopsis but information from agronomically important crops is limited. In the present work three full-length sequences encoding members of the GNAT/MYST family, namely HvMYST, HvELP3 and HvGCN5, respectively, were isolated and characterized from barley (Hordeum vulgare L.), a crop of high economic value. Expression analysis of the barley GNAT/MYST genes revealed significant quantitative differences in different seed developmental stages and between cultivars with varying seed size and weight, suggesting an association of these genes with barley seed development. Furthermore, all three HvGNAT/MYST genes were inducible by the stress-related phytohormone abscisic acid (ABA) involved in seed maturation, dormancy and germination, implying a possible regulation of these genes by ABA, during barley seed development, germination and stress response.     

Plant 2-arylobenzofurans demonstrate a selective estrogen receptor modulator profile

We have isolated from the plant Onobrychis ebenoides three novel arylobenzofurans with binding affinity for the estrogen receptor. In this study, we evaluated these arylobenzofurans, namely ebenfuran I, ebenfuran II and ebenfuran III for their potential selective estrogen receptor modulator (SERM)-like properties. We examined their ability, (1) to induce the insulin growth factor binding protein-3 (IGFBP-3) in MCF-7 breast cancer cells, (2) to stimulate differentiation and mineralization of osteoblastic cell culture by histochemical staining for alkaline phosphatase, Alizarin Red-S staining and calcium levels in the supernatants and (3) to inhibit cell proliferation of cervical adenocarcinoma (Hela) cells by use of the MTT assay. An estrogen receptor mediated effect was investigated by carrying out chloramphenicol acetyl transferase (CAT) assay on transient MCF-7 transfectants. Estradiol and the "pure" antiestrogen ICI 182780 were included to serve as control samples of the estrogenic and antiestrogenic effect respectively. Our data reveal that ebenfuran II is a highly potent SERM, exhibiting antiestrogenic activity in breast cancer cells via the estrogen receptor, estrogenic effect on osteoblasts and no stimulatory effect on cervix adenocarcinoma cells. In conclusion, our study is the first to demonstrate that plant derived arylobenzofurans show a SERM profile and may be considered for the prevention and treatment of diseases such as breast cancer, cervical cancer and osteoporosis.     

Fine needle aspiration of borderline ovarian lesions. Is It useful?

Borderline ovarian tumors are a low grade form of epithelial ovarian carcinoma with a low rate of growth and a low potential to invade or metastasize. According to the new World Health Organization classification, these tumors are placed between clearly benign and obviously malignant tumors because they exhibit some, but not all, of the morphologic features of malignancy. For a distinction between borderline lesions and cystadenomas or carcinomas, 2 criteria are of the utmost importance: presence of nuclear atypia and absence of stromal invasion. The pathologic subtype ofperitoneal implants is probably one of the main prognosticfactors in patients with serous tumors of low malignant potential, while the prognostic value of micropapillary serous carcinoma in patients with noninvasive implants remains debatable. Although fine needle aspiration (FNA) is the most accurate diagnostic method in cytopathology, its value in the diagnosis of borderline lesions is limited, mainly because of its inability to establish the absence of stromal invasion. The diagnostic accuracy of RNA can be improved by supplementing cytologic examination with such diagnostic techniques as immunocytochemistry and cytometry.     

Quantitative structure activity relationships (QSAR) of substituded (S)-phenylpiperidines as preferential dopamine autoreceptor antagonists

A QSAR analysis for substituted (S)-phenylpiperidines as dopamine (DA) antagonists is described. The studied derivatives differ at the nitrogen substitutent (R) and at the substitutents (X) of the phenyl-ring. The analysis was done using the C-QSAR suite program (Biobyte) through the Internet. Clog P, CMR, M(vol), B1 and L (the Verloop's sterimol parameters for the substitutents) were used as parameters. In all the three studied cases clog P plays a significant part in the QSAR of DA antagonists, followed by the steric factors. In one case the electronic effect contributes significantly.     

Real-time simulation of hand motion for prosthesis control

Individuals with hand amputation suffer substantial loss of independence. Performance of sophisticated prostheses is limited by the ability to control them. To achieve natural and simultaneous control of all wrist and hand motions, we propose to use real-time biomechanical simulation to map between residual EMG and motions of the intact hand. Here we describe a musculoskeletal model of the hand using only extrinsic muscles to determine whether real-time performance is possible. Simulation is 1.3 times faster than real time, but the model is locally unstable. Methods are discussed to increase stability and make this approach suitable for prosthesis control.