A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Evidence-informed urban health and sustainability governance in two Chinese cities

Sustainable development is best supported by intersectoral policies informed by a range of evidence and knowledge types (e.g. scientific and lay). Given China’s rapid urbanisation, scale and global importance in climate mitigation, this study investigates how evidence is perceived and used to inform urban health and sustainability policies at central and local levels. Well-informed senior professionals in government/scientific agencies (12 in Beijing and 11 in Ningbo) were interviewed. A thematic analysis is presented using deductive and inductive coding. Government agency participants described formal remits and processes determining the scope and use of evidence by different tiers of government. Academic evidence was influential when commissioned by government departments. Public opinion and economic priorities were two factors that also influenced the use or weight of evidence in policymaking. This study shows that scientific evidence produced or commissioned by government was routinely used to inform urban health and sustainability policy. Extensive and routine data collection is regularly used to inform cyclical policy processes, which improves adaptive capacity. This study contributes to knowledge on the ‘cultures of evidence use’. Environmental governance can be further improved through increased data-sharing and use of diverse knowledge types

Development of the ECOSAR P-Band Synthetic Aperture Radar

This paper describes objectives and recent progress on the development of the EcoSAR, a new P-band airborne radar instrument being developed at the NASA/ Goddard Space Flight Center (GSFC) for the polarimetric and interferometric measurements of ecosystem structure and biomass. These measurements support science requirements for the study of the carbon cycle and its relationship to climate change. The instrument is scheduled to be completed and flight tested in 2013. Index Terms SAR, Digital Beamforming, Interferometry

Cataclysmic Variables in the First Year of the Zwicky Transient Facility

Using selection criteria based on amplitude, time, and color, we have identified 329 objects as known or candidate cataclysmic variables (CVs) during the first year of testing and operation of the Zwicky Transient Facility. Of these, 90 are previously confirmed CVs, 218 are strong candidates based on the shape and color of their light curves obtained during 3–562 days of observation, and the remaining 21 are possible CVs but with too few data points to be listed as good candidates. Almost half of the strong candidates are within 10 deg of the galactic plane, in contrast to most other large surveys that have avoided crowded fields. The available Gaia parallaxes are consistent with sampling the low mass transfer CVs, as predicted by population models. Our follow-up spectra have confirmed Balmer/helium emission lines in 27 objects, with four showing high-excitation He ii emission, including candidates for an AM CVn, a polar, and an intermediate polar. Our results demonstrate that a complete survey of the Galactic plane is needed to accomplish an accurate determination of the number of CVs existing in the Milky Way

Global and exponential attractors for a Ginzburg-Landau model of superfluidity

The long-time behavior of the solutions for a non-isothermal model in superfluidity is investigated. The model describes the transition between the normal and the superfluid phase in liquid 4He by means of a non-linear differential system, where the concentration of the superfluid phase satisfies a non-isothermal Ginzburg-Landau equation. This system, which turns out to be consistent with thermodynamical principles and whose well-posedness has been recently proved, has been shown to admit a Lyapunov functional. This allows to prove existence of the global attractor which consists of the unstable manifold of the stationary solutions. Finally, by exploiting recent techniques of semigroups theory, we prove the existence of an exponential attractor of finite fractal dimension which contains the global attractor.Comment: 39 page

Limitations of perturbative techniques in the analysis of rhythms and oscillations

Perturbation theory is an important tool in the analysis of oscillators and their response to external stimuli. It is predicated on the assumption that the perturbations in question are “sufficiently weak”, an assumption that is not always valid when perturbative methods are applied. In this paper, we identify a number of concrete dynamical scenarios in which a standard perturbative technique, based on the infinitesimal phase response curve (PRC), is shown to give different predictions than the full model. Shear-induced chaos, i.e., chaotic behavior that results from the amplification of small perturbations by underlying shear, is missed entirely by the PRC. We show also that the presence of “sticky” phase–space structures tend to cause perturbative techniques to overestimate the frequencies and regularity of the oscillations. The phenomena we describe can all be observed in a simple 2D neuron model, which we choose for illustration as the PRC is widely used in mathematical neuroscience

Herschel/HIFI deepens the circumstellar NH3 enigma

Circumstellar envelopes (CSEs) of a variety of evolved stars have been found to contain ammonia (NH3) in amounts that exceed predictions from conventional chemical models by many orders of magnitude. The observations reported here were performed in order to better constrain the NH3 abundance in the CSEs of four, quite diverse, oxygen-rich stars using the NH3 ortho J_K = 1_0 - 0_0 ground-state line. We used the Heterodyne Instrument for the Far Infrared aboard Herschel to observe the NH3 J_K = 1_0 - 0_0 transition near 572.5 GHz, simultaneously with the ortho-H2O J_Ka,Kc = 1_1,0 -1_0,1 transition, toward VY CMa, OH 26.5+0.6, IRC+10420, and IK Tau. We conducted non-LTE radiative transfer modeling with the goal to derive the NH3 abundance in these objects' CSEs. For the latter two stars, Very Large Array imaging of NH3 radio-wavelength inversion lines were used to provide further constraints, particularly on the spatial extent of the NH3-emitting regions. Results. We find remarkably strong NH3 emission in all of our objects with the NH3 line intensities rivaling those obtained for the ground state H2O line. The NH3 abundances relative to H2 are very high and range from 2 x 10-7 to 3 x 10-6 for the objects we have studied. Our observations confirm and even deepen the circumstellar NH3 enigma. While our radiative transfer modeling does not yield satisfactory fits to the observed line profiles, it leads to abundance estimates that confirm the very high values found in earlier studies. New ways to tackle this mystery will include further Herschel observations of more NH3 lines and imaging with the Expanded Very Large Array.Comment: 4+2 page

A kilometer-scale asteroid inside Venus's orbit

Near-Earth asteroid population models predict the existence of asteroids located inside the orbit of Venus. However, despite searches up to the end of 2019, none have been found. Here we report the discovery by the Zwicky Transient Facility of the first known asteroid located inside of Venus' orbit, 2020 AV₂, possessing an aphelion distance of 0.65 au and ∼2 km in size. While it is possible that 2020 AV₂ is the largest of its kind, we find that its discovery is surprising in the context of population models where the expected count is close to zero. If this discovery is not a statistical fluke, then 2020 AV₂ may come from a yet undiscovered source population of asteroids interior to Venus, and currently favored asteroid population models may need to be adjusted

A kilometer-scale asteroid inside Venus's orbit

Near-Earth asteroid population models predict the existence of asteroids located inside the orbit of Venus. However, despite searches up to the end of 2019, none have been found. Here we report the discovery by the Zwicky Transient Facility of the first known asteroid located inside of Venus' orbit, 2020 AV₂, possessing an aphelion distance of 0.65 au and ∼2 km in size. While it is possible that 2020 AV₂ is the largest of its kind, we find that its discovery is surprising in the context of population models where the expected count is close to zero. If this discovery is not a statistical fluke, then 2020 AV₂ may come from a yet undiscovered source population of asteroids interior to Venus, and currently favored asteroid population models may need to be adjusted

Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma

Kaposi's sarcoma (KS) is the major AIDS-associated malignancy. It is characterized by the proliferation of spindle cells, inflammatory infiltrate, and aberrant angiogenesis caused by Kaposi's sarcoma herpesvirus (KSHV) infection. Small GTPase Rac1, an inflammatory signaling mediator triggering reactive oxygen species (ROS) production by NADPH-oxidases, is implicated in carcinogenesis and tumor angiogenesis. Here, we show that expression of a constitutively active Rac1 (RacCA) driven by the α-smooth muscle actin promoter in transgenic mice is sufficient to cause KS-like tumors through mechanisms involving ROS-driven proliferation, up-regulation of AKT signaling, and hypoxia-inducible factor 1-α–related angiogenesis. RacCA-induced tumors expressed KS phenotypic markers; displayed remarkable transcriptome overlap with KS lesions; and were, like KS, associated with male gender. The ROS scavenging agent N-acetyl-cysteine inhibited angiogenesis and completely abrogated transgenic RacCA tumor formation, indicating a causal role of ROS in tumorigenesis. Consistent with a pathogenic role in KS, immunohistochemical analysis revealed that Rac1 is overexpressed in KSHV+ spindle cells of AIDS-KS biopsies. Our results demonstrate the direct oncogenicity of Rac1 and ROS and their contribution to a KS-like malignant phenotype, further underscoring the carcinogenic potential of oxidative stress in the context of chronic infection and inflammation. They define the RacCA transgenic mouse as a model suitable for studying the role of oxidative stress in the pathogenesis and therapy of KS, with relevance to other inflammation-related malignancies. Our findings suggest host and viral genes triggering Rac1 or ROS production as key determinants of KS onset and potential KS chemopreventive or therapeutic targets