RESUMO
Matriglycan, a recently characterized linear polysaccharide, is composed of alternating xylose and glucuronic acid subunits bound to the ubiquitously expressed protein α-dystroglycan (α-DG). Pathogenic arenaviruses, like the Lassa virus (LASV), hijack this long linear polysaccharide to gain cellular entry. Until recently, it was unclear through what mechanisms LASV engages its matriglycan receptor to initiate infection. Additionally, how matriglycan is synthesized onto α-DG by the Golgi-resident glycosyltransferase LARGE1 remained enigmatic. Recent structural data for LARGE1 and for the LASV spike complex informs us about the synthesis of matriglycan as well as its usage as an entry receptor by arenaviruses. In this review, we discuss structural insights into the system of matriglycan generation and eventual recognition by pathogenic viruses. We also highlight the unique usage of matriglycan as a high-affinity host receptor compared with other polysaccharides that decorate cells.
RESUMO
The mortality rate of newborns with severe congenital heart disease (CHD) has significantly decreased over the past few decades. However, many of these children experience neurological impairments, particularly following a hypoxic cardiac arrest. The use of extracorporeal membrane oxygenation (ECMO) has been considered an effective treatment for severe hypoxia in CHD cases. Various clinical studies have examined the use of ECMO for resuscitation after hypoxic cardiac arrest, but the results have been contradictory, showing a significant incidence of both mortality and morbidity in some studies while others report good outcome. In order to investigate the mechanisms behind brain injury associated with extracorporeal circulation, we have developed a neonatal porcine model of hypoxia-induced cardiac arrest followed by veno-arterial ECMO therapy.
Assuntos
Modelos Animais de Doenças , Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Hipóxia , Animais , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Parada Cardíaca/etiologia , Suínos , Hipóxia/terapia , Animais Recém-Nascidos , Ressuscitação/métodos , Reanimação Cardiopulmonar/métodosRESUMO
Pulmonary hypertension (PH) is a chronic and progressive disorder characterized by elevated mean pulmonary arterial pressure, pulmonary vascular remodeling, and the development of concentric laminar intimal fibrosis with plexiform lesions. While rodent models have been developed to study PH, they have certain deficiencies and do not entirely replicate the human disease due to the heterogeneity of PH pathology. Therefore, combined models are necessary to study PH. Recent studies have shown that altered pulmonary blood flow is a significant trigger in the development of vascular remodeling and neointimal lesions. One of the most promising rodent models for increased pulmonary flow is the combination of unilateral left pneumonectomy with a "second hit" of monocrotaline (MCT) or SU5416. The removal of one lung in this model forces blood to circulate only in the other lung and induces increased and turbulent pulmonary blood flow. This increased vascular flow leads to progressive remodeling and occlusion of small pulmonary arteries. The second hit by MCT or SU5416 leads to endothelial cell dysfunction, resulting in severe PH and the development of plexiform arteriopathy.
Assuntos
Modelos Animais de Doenças , Hipertensão Pulmonar , Indóis , Pulmão , Monocrotalina , Pirróis , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/induzido quimicamente , Animais , Ratos , Humanos , Pulmão/patologia , Pneumonectomia/métodos , Remodelação Vascular , Artéria Pulmonar/patologia , CamundongosRESUMO
Thin ferromagnetic films possessing perpendicular magnetic anisotropy derived from the crystal lattice can deliver the requisite magnetocrystalline anisotropy density for thermally stable magnetic memory and logic devices at the single-digit-nm lateral size. Here, we demonstrate that an epitaxial synthetic antiferromagnet can be formed from L10 FePd, a candidate material with large magnetocrystalline anisotropy energy, through insertion of an ultrathin Ir spacer. Tuning of the Ir spacer thickness leads to synthetic antiferromagnetically coupled FePd layers, with an interlayer exchange field upwards of 0.6 T combined with a perpendicular magnetic anisotropy energy of 0.95 MJ/m3 and a low Gilbert damping of 0.01. Temperature-dependent ferromagnetic resonance measurements show that the Gilbert damping is mostly insensitive to temperature over a range of 20 K up to 300 K. In FePd|Ir|FePd trilayers with lower interlayer exchange coupling, optic and acoustic dynamic ferromagnetic resonance modes are explored as a function of temperature. The ability to engineer low damping and large interlayer exchange coupling in FePd|Ir|FePd synthetic antiferromagnets with high perpendicular magnetic anisotropy could prove useful for high performance spintronic devices.
RESUMO
Species of Saccharomyces genus have played an irreplaceable role in alcoholic beverage and baking industry for centuries. S. cerevisiae has also become an organism of choice for industrial production of alcohol and other valuable chemicals and a model organism shaping the rise of modern genetics and genomics in the past few decades. Today´s brewing industry faces challenges of decreasing consumption of traditional beer styles and increasing consumer demand for new styles, flavors and aromas. The number of currently used brewer's strains and their genetic diversity is yet limited and implementation of more genetic and phenotypic variation is seen as a solution to cope with the market challenges. This requires modification of current production strains or introduction of novel strains from other settings, e.g. industrial or wild habitats into the brewing industry. Due to legal regulation in many countries and negative customer perception of GMO organisms, the production of food and beverages requires non-GMO production organisms, whose development can be difficult and time-consuming. Here, we apply FIND-IT (Fast Identification of Nucleotide variants by DigITal PCR), an ultrafast genome-mining method, for isolation of novel yeast variants with varying flavor profiles. The FIND-IT method uses combination of random mutagenesis, droplet digital PCR with probes that target a specific desired mutation and a sub-isolation of the mutant clone. Such an approach allows the targeted identification and isolation of specific mutant strains with eliminated production of certain flavor and off-flavors and/or changes in the strain metabolism. We demonstrate that the technology is useful for the identification of loss-of function or gain of function mutations in unrelated industrial and wild strains differing in ploidy. Where no other phenotypic selection exists, this technology serves together with standard breeding techniques as a modern tool facilitating a modification of (brewer's) yeast strains leading to diversification of the product portfolio.
Assuntos
Cerveja , Engenharia Metabólica , Saccharomyces , Cerveja/microbiologia , Saccharomyces/genética , Saccharomyces/metabolismo , Aromatizantes/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genéticaRESUMO
Three-dimensional covalent connectors are valuable synthons for accessing crystalline or amorphous networks. Currently, fused polycyclic alkanes are employed as connectors in this context. We debut phosphorus-nitrogen (PN) cages as new 3-dimensional (3-D) inorganic connectors that yield crystalline and amorphous networks, including examples with gas porosity. We show that the high tunability of PN cages accelerates network diversification and the presence of a responsive 31P NMR spectroscopic handle provides structural insight. Collectively, this work unlocks a new and convenient 3-D synthon for reticular chemistry.