An outstanding biological question is why tissue regeneration in mammals is limited, whereas urodele amphibians and teleost fish regenerate major structures, largely by cell cycle reentry. Upon ...inactivation of Rb, proliferation of postmitotic urodele skeletal muscle is induced, whereas in mammalian muscle this mechanism does not exist. We postulated that a tumor suppressor present in mammals but absent in regenerative vertebrates, the Ink4a product ARF (alternative reading frame), is a regeneration suppressor. Concomitant inactivation of Arf and Rb led to mammalian muscle cell cycle reentry, loss of differentiation properties, and upregulation of cytokinetic machinery. Single postmitotic myocytes were isolated by laser micro-dissection-catapulting, and transient suppression of Arf and Rb yielded myoblast colonies that retained the ability to differentiate and fuse into myofibers upon transplantation in vivo. These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration.
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4Inactivation of Rb and ARF induces cell cycle reentry of mammalian muscle 4Single postmitotic myocytes give rise to clones after transient loss of Rb and ARF 4Myocyte-derived clones differentiate and fuse to mature muscle fibers in vivo 4Regeneration by reversal of differentiation is possible in mammalian cells
Strobes are pyrotechnic compositions which show an oscillatory combustion; a dark phase and a flash phase alternate periodically. The strobe effect has applications in various fields, most notably in ...the fireworks industry and in the military area. All strobe compositions mentioned in the literature were discovered by trial and error methods and the mechanisms involved remain unclear. Many oscillatory systems such as Belousov–Zhabotinsky reactions, cool flames, self‐propagating high‐temperature synthesis have been observed and theories developed to elucidate their unstable behavior based on chemical interactions or based on physical processes. These systems are compared to experimental observations made on strobe mixtures.
Flash dance: Strobes are pyrotechnic compositions which burn in an oscillatory manner: a dark and a flash phase alternate periodically (see scheme). They have various applications in the fireworks industry and also as flares. However, their mechanism is not well understood. A few better understood oscillatory systems (Belousov–Zhabotinsky reactions, cool flames, self‐propagating high‐temperature synthesis) are compared to observations made on strobe mixtures.
Single Ni1–x Cu x TiO3 (0.05 ≤ x ≤ 0.2) Ilmenite-type phases were successfully prepared through a solid-state reaction route using divalent metal nitrates as precursors and characterized. Their ...electrocatalytic performance for oxygen evolution reaction (OER) in alkaline media is presented. The Cu content was determined (0.05 ≤ x ≤ 0.2) by X-ray diffraction. A thorough powder neutron diffraction study was carried out to identify the subtle changes caused by copper substitution in the structure of NiTiO3. The evolution of the optical and magnetic properties with the Cu content was also investigated on the raw micrometer-sized particles. A reduction in particle size down to ≈15 nm was achieved by ball-milling the raw powder prepared by the solid-state reaction. The best catalytic activity for OER was obtained for nanometer-sized particles of Ni0.8Cu0.2TiO3 drop-casted on the Cu plate. For this electrode, a current density of 10 mA cm–2 for oxygen production was generated at 345 and 470 mV applied overpotentials with 1 and 0.1 M NaOH solutions as electrolytes, respectively. The catalyst retained this OER activity at 10 mA cm–2 for long-term electrolysis with a faradic efficiency of 90% for O2 production in a 0.1 M NaOH electrolyte.
Diseases caused by Aedes-borne viruses, such as dengue, Zika, chikungunya, and yellow fever, are emerging and reemerging globally. The causes are multifactorial and include global trade, ...international travel, urbanisation, water storage practices, lack of resources for intervention, and an inadequate evidence base for the public health impact of Aedes control tools. National authorities need comprehensive evidence-based guidance on how and when to implement Aedes control measures tailored to local entomological and epidemiological conditions.
This review is one of a series being conducted by the Worldwide Insecticide resistance Network (WIN). It describes a framework for implementing Integrated Aedes Management (IAM) to improve control of diseases caused by Aedes-borne viruses based on available evidence. IAM consists of a portfolio of operational actions and priorities for the control of Aedes-borne viruses that are tailored to different epidemiological and entomological risk scenarios. The framework has 4 activity pillars: (i) integrated vector and disease surveillance, (ii) vector control, (iii) community mobilisation, and (iv) intra- and intersectoral collaboration as well as 4 supporting activities: (i) capacity building, (ii) research, (iii) advocacy, and (iv) policies and laws.
IAM supports implementation of the World Health Organisation Global Vector Control Response (WHO GVCR) and provides a comprehensive framework for health authorities to devise and deliver sustainable, effective, integrated, community-based, locally adapted vector control strategies in order to reduce the burden of Aedes-transmitted arboviruses. The success of IAM requires strong commitment and leadership from governments to maintain proactive disease prevention programs and preparedness for rapid responses to outbreaks.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these ...mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Childhood muscle-related cancer rhabdomyosarcoma is a rare disease with a 50-year unmet clinical need for the patients presented with advanced disease. The rarity of ∼350 cases per year in North ...America generally diminishes the viability of large-scale, pharmaceutical industry driven drug development efforts for rhabdomyosarcoma. In this study, we performed a large-scale screen of 640,000 compounds to identify the dihydropyridine (DHP) class of anti-hypertensives as a priority compound hit. A structure-activity relationship was uncovered with increasing cell growth inhibition as side chain length increases at the ortho and para positions of the parent DHP molecule. Growth inhibition was consistent across n = 21 rhabdomyosarcoma cell line models. Anti-tumor activity in vitro was paralleled by studies in vivo. The unexpected finding was that the action of DHPs appears to be other than on the DHP receptor (i.e., L-type voltage-gated calcium channel). These findings provide the basis of a medicinal chemistry program to develop dihydropyridine derivatives that retain anti-rhabdomyosarcoma activity without anti-hypertensive effects.
•640,000 compounds were screened for potential hits, leads or therapeutic agents for treating rhabdomyosarcoma.•The dihydropyridine (DHP) class of anti-hypertensives were found to be priority compound hits.•The DHP drug azelnidipine was selected as a lead compound for consistent anti-tumor cell activity.•Anti-tumor activity of azelnidipine in vitro was paralleled by studies in vivo.•The action of the DHP drugs was found to be other than on the DHP receptor (i.e., L-type voltage-gated calcium channel).
The bis (tetra-ethylammonium) tetraiodo-zincate (II) was prepared by slow evaporation an aqueous stoichiometric mixture of tetra-ethylammonium iodide and zinc iodide at room temperature. This ...compound has been characterized by X-ray diffraction (XRD), thermal analysis, UV–vis spectroscopy and complex impedance spectroscopy. Single crystal X-ray diffraction analysis shows that the title compound crystallizes in the tetragonal system with space group P4¯21m.The differential thermal analysis (DTA) and temperature-controlled X-ray diffraction study reveal a reversible first order phase transition at about 444 K between low temperature-tetragonal and high temperature-orthorhombic forms of (C2H5)4N2ZnI4. Below 444 K, the low temperature form exhibits two linear regimes of thermal expansion with a change in the slope around 373 K which is ascribed to a second-order phase transition. The diffuse reflectance indicates the existence of an optical direct transition with the band gap energy is equal to 3.9 eV. The spectra of complex impedances obtained in the temperature range from 403 to 468 K were modelled by a combination of R//CPE elements. . A change of conduction regime around 444 K is noted in the variation of the Ln (σDC.T) versus reciprocal temperature. In both regimes, the conductivity obeys the Arrhenius law with activation energies of 1.37 eV in regime I and 2.37 eV in regime II. Frequency dependence of the AC conductivity followed the universal Jonscher's power law.
Intermolecular hydrogen bonds of (C2H5)4N2ZnI4 compoundXRPD patterns recorded during heating of the (C2H5)4N2ZnI4 powder in air from RT to 473 K. Display omitted
•Single crystals (C2H5)4N2ZnI4 were obtained by slow evaporation method.•The cohesion of the structure is ensured by hydrogen bonds and electrostatic interactions.•This material undergoes a structural phase transition of the first order at 444 K.•This semi-conducting organic–inorganic Zn-based compound has a band gap of 3.9 eV.•The electrical conduction mechanism was investigated.
Abstract
Solar flares are regularly detected by the Large Area Telescope (LAT) on board the Fermi satellite, however no γ-ray emission from other stellar eruptions has ever been captured. The Swift ...detection in 2014 April of a powerful outburst originating from DG CVn, with associated optical and radio emissions, enticed us to search for possible 0.1–100 GeV emission from this flaring nearby binary star using the Fermi/LAT. No γ-ray emission is detected from DG CVn in 2014, but we report a significant γ-ray excess in 2012 November, at a position consistent with that of the binary. There are no reports of contemporary flaring at other wavelengths from DG CVn or any other source within the error circle of the γ-ray source. We argue that the γ-ray flare is more likely to have been associated with a background blazar than with DG CVn and identify a candidate for follow-up study.
The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. ...albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control.
This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors.
Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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