Статті в журналах з теми "681.2:621.3.082.1"

1. INTRODUCTION 681.1 Receptor patterns in the plasma membrane 681.2 Different types of receptor patterns 712. METHODS TO INVESTIGATE NON-RANDOM RECEPTOR CLUSTERING 732.1 Fluorescence resonance energy transfer 732.2 Flow cytometric energy transfer measurement 782.3 Fluorescence anisotropy and energy transfer 792.4 Photobleaching energy transfer on single cells 812.5 Two-dimensional mapping of receptor superstructures 822.6 Detecting single receptor molecules 852.7 Chemical identification of receptor clusters 862.8 Electron microscopy 872.9 Scanning force microscopy 883. CONFORMATIONAL STATES OF RECEPTORS 903.1 Multi-subunit receptor structures 903.2 Physical parameters influencing conformational states 913.3 Chemical interactions and receptor conformations 924. ON THE ORIGIN OF NATURALLY OCCURRING RECEPTOR CLUSTERS 934.1 Synthesis of receptors and their localization in the plasma membrane 934.2 Lipid domain structure of the plasma membrane 944.3 The validity of the Singer–Nicolson model 945. CONCLUSIONS 966. ACKNOWLEDGEMENTS 967. REFERENCES 97

Preliminary research conducted in Warsaw in the 1970s and 2000s showed that roe deer (Capreolus capreolus) stayed in forest habitat and avoided anthropogenic areas. Activity and exploration patterns of animals are shaped by indices of anthropogenic disturbances, elevated in large cities. The aims of the study were (1) to compare the presence of roe deer in natural and anthropogenic habitats of Warsaw during three periods: 1976–1978, 2005–2008 and 2017–2021, based on snow tracking on transect routes (681.2 km in total), and (2) to describe the presence and activity of roe deer in relation to human disturbances in selected urban forests in its reproductive period (March–August), based on camera trap survey (2019–2020, 859 observations, 5317 trap-days in total). The number of tracks was higher in natural habitat during all three periods, with the highest value in 2017–2021 (9.85/km/24h). The peak of roe deer activity was recorded at dusk, and it changed with moon phases between spring and summer. Landscape connectivity and level of light pollution did not affect the activity pattern of roe deer. Our research showed that roe deer inhabiting urban areas avoided human presence by using well-covered habitats and being active in periods when the level of human disturbance was lower.

Buthūr Labaniyya (Acne vulgaris) is one of the oldest and commonest dermatological problem, which are known since antiquity and it has been called by different names in different parts of the world. It is a disorder of pilosebaceous unit which mainly affects the peripubertal population and clinically manifests as comedones (open/closed), papules, pustules, nodules, and cysts and heals with scars. As per Unani classics, Buthūr Labaniyya (Acne vulgaris) is termed as Muhāsā or Kīl characterised by small, white eruptions on the nose and cheeks, which resemble a condensed milk drop. Renowned Unani physicians Zakariyya Rāzī, Ibn Hubal, Ibn sīnā, Dā’ūd Antāki and Hakīm Akbar Arzānī have stated that, it is a dermatological disorder of adolescents that present as whitish eruptions over the face caused by M’ādda Sadīdiya (Suppurative material) or preponderance of Ghalīz (filthy) M’ādda Balghamiyya. Acne vulgaris affected 681.2 million people worldwide in 2016. This was a 10% rise from 612 million in 2006. Acne ranks eighth on the list of the world's most common diseases (9.4%) in 2010, with a worldwide prevalence of 645 million. In Unani Medicine, Buthūr Labaniyya (Acne vulgaris) is a well recognize disease entity and has been treated successfully since antiquity with various single and compound drugs having Jāli (Detergent), Muhalil (Resolvent) and Mujaffif (Desiccative), Musaffi-i Khūn advia properties. In this review, we tried to compile all the available information till date from both unani and other published scientific papers and textbooks which will fruitful for further research.

Ten natural dye yielding and two mordant plants were biochemically analyzed. Though natural dyes are widely used, information about the active principles responsible for dyeing is hardly available. In the present experiment, total chlorophyll, carotinoids, tannins, phenolics, flavonoids and curcumin were determined among the dye yielding plants, while K, S, P, Ca, Mg, Mn, Zn, Fe, Cu and Co were determined in the case of mordant plants. In Bixa orellana, used for yellow dyeing, the carotinoid content was 163.11 mg g-1 and in Clerodendrum chinense and Datura stramonium, which were used for green colouring, total chlorophyll content of 10.29 mg and 11.83 mg g-1 was recorded. Curcumin content responsible for orange colouring in Curcuma domestica was 27.7 mg g-1 while flavonoid content in Solanum nigrum and Terminalia chebula, which were used for brown, brown to black dyes was 24.89 and 21.73 mg g-1. Among the plants used for dyeing different colours, Punica granatum and Parkia timoriana were found to contain higher amounts of total phenols and bound phenols by recording 681.2 mg g-1 and 287.6 mg g-1 total phenols and 151.6 mg g-1 and 130.2mg g-1 bound phenols, while higher amounts of orthodihydric phenols and tannins were recorded in Punica granatum and Strobilanthes flaccidifolius by recording 20.11mg g-1 and 9.54mg g-1 orthodihydric phenols and 675.57mg g-1 and 648.12 mg g-1 tannins, respectively. In case of the plants used as mordant, higher contents of Ca, Mg, K, Zn, Fe and Mn were detected in Achyranthes aspera, while higher amounts of P, Fe and Cu were recorded in Garcinia xanthochymus.

The mixed potassium thio/oxo-orthovanadates(V) of the series K3[VSxO4−x] (x = 1, 2, 2.6, 3.4-4) and the sodium compound Na3[VSO3] have been prepared in evacuated silica ampoules at reaction temperatures of 450 to 600 °C starting from stoichiometric amounts of an alkali oxovanadate, the alkali sulfide and (where necessary) elemental vanadium and sulfur. The crystal structures (determined on the basis of X-ray single-crystal data) of the yellow compounds Na3[VSO3] (space group R3c, a = 863.3(3), c = 1234.7(3) pm, Z = 6, R1 = 0.0170) and K3[VSO3] (space group P21/m, a = 659.0(3), b = 589.5(3), c = 879.3(3) pm, β = 102.12(3)°, Z = 2, R1 = 0.0907) both contain isolated monothio-vanadate ions [VSO3]3−. The orange crystals of K3[VS2O2] (space group P21/m, a = 1056(2), b = 732.2(10), c = 1167(2) pm, β = 121.86(11)°, Z = 4, R1 = 0.0977) as well as the red phase K3[VS2.6O1.4] (space group P21/c, a = 1009.1(6), b = 681.2(4), c = 1190.1(8) pm, β = 93.55(1)°, Z = 4, R1 = 0.0929) also crystallize with new, singular, monoclinic structure types, which are nevertheless structurally related, as indicated by the similar lattice parameters. Starting from K3[VS4], a phase width up to the composition K3[VS3.4O0.6] (space group Pnma, a = 909.5(3), b = 1035.6(5), c = 895.6(6) pm, Z = 4, R1 = 0.0948) is observed in addition. Structure and bonding in this new series of potassium compounds are discussed and compared with those in the respective sodium phases, including aspects like anion geometry and dynamics (as observed by Raman spectroscopy), packing in the crystals, UV/Vis spectroscopy and FP-LAPW band structure calculations.

Mangalarga, due to its marching abilities, is the mostly widespread and numerous equine breed in Brazil. Furthermore, previous studies indicate that the semen of these horses is particularly susceptible to cryo-injuries. Therefore, the use of chilled semen is crucial when employing reproductive biotechnologies. However, previous studies indicate that chilled semen is highly impaired by the oxidative stress, which is caused by reactive oxygen species (ROS). An alternative to overcome the injuries caused by oxidative stress is antioxidant treatment, which requires the identification of those ROS that are the most deleterious. The aim of this study was to identify the most harmful ROS to Mangalarga sperm. Semen samples from 4 horses were collected, mixed with chilling media (Equimix®, Nutricell) and transported to the laboratory at 15°C. Samples were then incubated (1 h, 37°C) with 4 ROS inducing mechanisms: xanthine/xanthine oxidase (produces superoxide anion), hydrogen peroxide (4 mM), ascorbate and ferrous sulfate (4 mM; produces hydroxyl radical). Samples were analysed for motility using computer assisted sperm analysis (CASA). The 3-3′ diaminobenzidine stain was used as an index of mitochondrial activity, the eosin nigrosin stain as an index of membrane integrity, the simple stain (fast green/Bengal rose) as an index of acrosome integrity, sperm chromatin structure assay (SCSA) as an index of DNA fragmentation, and the measurement of thiobarbituric acid reactive substances (TBARS) an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). Results showed that Mangalarga sperm is highly susceptible to the hydroxyl radical. Samples treated with this ROS showed a lower percentage of sperm with high mitochondrial activity then samples treated with hydrogen peroxide (24.6 ± 5.9 v. 43.7 ± 6.8%, respectively). Similarly, lipid peroxidation (TBARS) was higher in samples treated with hydroxyl radical when compared with those treated with both superoxide anion and hydrogen peroxide (2037.7 ± 154.8, 681.2 ± 170.1, and 789.4 ± 124.5 ng/106 sperm). In addition, for all variables analysed using CASA except for ALH and BCF, samples treated with hydroxyl radical showed decreased quality when compared with the other samples. A positive correlation was found between TBARS and mitochondrial activity, indicating that the higher the sperm susceptibility of sperm against oxidative stress, the lower the mitochondrial activity. Level of TBARS also correlated negatively with most of the variables evaluated by CASA. The present results suggest that Mangalarga sperm is highly susceptible to the hydroxyl radical, a mechanism apparently related to the mitochondrial activity. Therefore, an alternative to overcome the deleterious influence of oxidative stress in semen of Mangalarga stallions would be the treatment with hydroxyl radical scavengers such as vitamins C and E, reduced glutathione, and other nonenzymatic antioxidants. The authors acknowledge Nutricell for the media used and CAPES for financial support.

Abstract Abstract 311 Background: Identification of a dominant gain-of-function mutation in a JAK2 kinase, JAK2V617, in myeloproliferative diseases such as polycythemia vera (PV) and essential thrombocythemia (ET), provided the foundation for the development of a molecularly targeted therapy for these diseases. Exaggerated JAK2 signaling is believed to play a dominant role in PV and ET by driving unchecked differentiation and proliferation of erythrocyte and thrombocyte precursors. While PV and ET are managed by phlebotomy and/or cytoreductive therapies such as hydroxyurea and anagrelide in the majority of patients, patients who fail these treatments have limited therapeutic options. INCB018424, a potent, selective inhibitor of JAK1 and JAK2, with demonstrated efficacy in MF (PMF, post-PV & post-ET MF), was evaluated for clinical activity in patients refractory to or intolerant of treatment with hydroxyurea. Methods: A phase II trial of INCB018424 is being conducted in advanced PV (n= 34) and ET (n=39) patients. Following an initial phase in which three dose regimens; 10 mg BID, 25 mg BID, and 50 mg QD; were evaluated in each patient population (n=6-8/dose), starting doses of 10 mg BID in PV patients and 25 mg BID in ET patients were chosen based on efficacy and tolerability to explore in an expansion cohort. Dose modifications were allowed to normalize Hct, platelet, and WBC counts. Clinico-hematological response criteria as defined by Barosi et al. (Blood, 2009) were used to assess response. PK and PD data are being collected. Results: PV patients: 34 patients have completed 3 months of treatment; 20 have completed ≥ six months of treatment. 94% of patients have achieved PR or CR. Greater than 75% of patients have at least 2 of 3 hematological parameters (Hct %, platelet count, WBC count) within normal ranges vs 38% of patients at baseline. Mean Hct% was 46.5 ± 4.3 (mean ± SD) at baseline; 37.5 ± 4.6 at month 3; and 39 ± 3.9 at month 6. Mean WBC count (109/L) was 15.2 ± 10.3 at baseline: 9.8 ± 6.1 at month 3; and 10.4 ± 5.5 at month 6. Mean platelet count (× 109/L) was 553 ± 231 at baseline: 378 ± 158 at month 3; and 311 ± 127 at month 6. 24 patients were phlebotomy-dependent in the 6 months prior to study; all became phlebotomy independent within two weeks of initiating INCB018424. 21 patients had palpable splenomegaly at baseline, ranging from 1 to 21 cm below the costal margin (9.1 ± 5.3 cm). 60% experienced a ≥ 50% reduction in spleen size in the first month which has been sustained over the duration of treatment. In 57% of patients with splenomegaly, spleens became non-palpable. All patients with pruritus (n=26) have experienced rapid, statistically significant, and sustained improvement. Marked improvement was noted in bone pain, night sweats, and fever. AEs of at least Grade 2 severity reported in more than 1 patient were anemia (12%) and thrombocytopenia (6%) all of which were reversible upon dose interruption or modification. ET patients: 39 patients completed 3 months of treatment; 17 patients have completed ≥ 6 months of treatment; 3 have discontinued. 61% of patients have achieved PR or CR. Greater than 50% of patients have at least 2 of 3 hematological parameters (Hct%, platelet count, WBC count) within normal ranges. Mean platelet counts (× 109/L) were 1059 ± 517 at baseline; 578 ± 435 at month 1; 681.2 ± 250.8 at month 3; and 584.4 ± 151 at month 6. Mean WBC count (× 109/L) was 9.3 ± 5.3 at baseline: 7.4 ± 2.7 at month 3; and 6.9 ± 1.4 at month 6. Of four patients with splenomegaly, all have a > 50% reduction in spleen size. Marked improvement was noted in bone pain, pruritus, weakness, night sweats and abnormal finger sensations. AEs of at least Grade 2 severity reported in more than 1 patient were anemia (18%) and neutropenia (6%) all of which were reversible upon dose interruption or modification. Conclusions: In PV patients, normalization of hematology parameters with elimination of the need for phlebotomy, marked decreases in splenic volume, and significant effects on symptoms have been demonstrated. Similar changes were noted in ET patients. Given that leukocytosis is an independent risk factor for thrombosis in PV and in ET, the lowering of WBC counts described in this study may be associated with additional clinical benefit along with normalization of Hct% in PV and decreases in platelet counts in ET patients. In this study, INCB018424 is a well tolerated, effective therapy in patients with advanced PV and ET refractory to hydroxyurea treatment. Disclosures: Verstovsek: AstraZeneca: Research Funding; Exelixis: Research Funding; Incyte: Research Funding; Cephalon: Research Funding; SBIO: Research Funding. Off Label Use: INCB081424 from Incyte, XL019 from Exelixis, AZD1480 from AstraZeneca, CEP701 from Cephalon, SB1518 from SBIO. All ar JAK2 inhibitors and are investigational agents.. Rambaldi:Diasorin S.p.A.: Consultancy, Honoraria. Rosen:Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Southern California Lymphoma Group, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen : Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Tower Cancer Research Foundation: Employment. Levy:Incyte Corporation: Employment, Equity Ownership. Bradley:Incyte Corporation: Employment, Equity Ownership. Schacter:Incyte Corporation: Employment, Equity Ownership. Garrett:Incyte Corporation: Employment. Vaddi:Incyte Corporation: Employment, Equity Ownership. Contel:Incyte Corporation: Employment, Equity Ownership.