Barrier-properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

Nup98 FG repeat domains comprise hydrophobic FG motifs linked through uncharged spacers. FG motifs capture nuclear transport receptors (NTRs) during nuclear pore complex (NPC) passage, confer inter-repeat cohesion, and condense the domains into a selective phase with NPC-typical barrier properties. We found that shortening inter-FG spacers enhances cohesion, increases phase density, and tightens such barrier – consistent with a sieve-like phase. Phase separation tolerated mutations of Nup98-typical GLFG motifs, provided the domain-hydrophobicity remained preserved. NTR-entry, however, was sensitive to (certain) deviations from canonical FG motifs, suggesting a co-evolutionary adaptation. Unexpectedly, we found that arginines promote efficient FG-phase entry also by means other than cation-π interactions. Although incompatible with NTR·cargo complexes, a YG phase displayed remarkable transport selectivity, particularly for evolved GFPNTR-variants. GLFG to FSFG mutations made the FG phase hypercohesive, precluding NTR-entry. Longer spacers relieved this hypercohesive phenotype. The antagonism between cohesion and NTR·FG interactions appears thus key to transport selectivity

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.We thank Miguel Sánchez for text editing. We thank Erika R. Geisbrecht, Kenneth Irvine, and Ariberto Fassati for kindly providing reagents. This study was supported by grants from the Spanish Ministry of Science and Innovation (MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ARDF/FEDER) “A way to make Europe” (PID2020-118658RB-I00, SAF2017-83130-R, IGP-SO grant MINSEV1512-07-2016, CSD2009-0016 and BFU2016-81912-REDC), Comunidad Autónoma de Madrid (Tec4Bio-CM, S2018/NMT¬4443), Fundació La Marató de TV3 (201936-30-31), “La Caixa” Foundation (HR20-00075) and AECC (PROYE20089DELP) all to M.A.d.P. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 641639. M.G.G. and L.S. are sponsored by FPU fellowships (FPU15/03776 and FPU18/05394, respectively). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICIIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence CEX2020-001041-S

Managing student mental health: The challenges faced by academics on professional health care courses

To explore how academics on nursing and healthcare programmes are managing their roles and responsibility in relation to student mental health. There is growing concern about the mental health of university students in general and healthcare students in particular. Shifts in Higher Education policy, encouraging a ‘whole university approach,’ may place greater responsibility for student mental health on academics. However, little is known about the challenges that poor student mental health creates for academics on healthcare programmes. A qualitative approach, using semi‐structured interviews and focus groups, provided the opportunity for in‐depth analysis. Fourteen academics on healthcare programmes, including seven lecturers from nursing programmes, were interviewed between May and June 2017. Constant comparison analysis was followed to support grounded theory. Four key themes emerged. Academics had difficulty identifying and maintaining boundaries due to competing academic and professional identities. Student disclosures are accompanied by challenges arising due to professional responsibilities. Supporting student mental health on placement is difficult. Academics are aware and concerned about the potential negative impact of course content and practice on student mental health. This is the first study to explore in‐depth the challenges faced by academics on healthcare programmes by the rising prevalence of and concern for, student mental health. The findings indicate that leaders of nursing education programmes and their managers, need to be aware that academics face complex challenges in managing and responding student mental health and may struggle to maintain boundaries due, in part, to competing professional identities.Part funded by University of Derby VC Ideas Foru

The benefits of very low earth orbit for earth observation missions

Very low Earth orbits (VLEO), typically classified as orbits below approximately 450 km in altitude, have the potential to provide significant benefits to spacecraft over those that operate in higher altitude orbits. This paper provides a comprehensive review and analysis of these benefits to spacecraft operations in VLEO, with parametric investigation of those which apply specifically to Earth observation missions. The most significant benefit for optical imaging systems is that a reduction in orbital altitude improves spatial resolution for a similar payload specification. Alternatively mass and volume savings can be made whilst maintaining a given performance. Similarly, for radar and lidar systems, the signal-to-noise ratio can be improved. Additional benefits include improved geospatial position accuracy, improvements in communications link-budgets, and greater launch vehicle insertion capability. The collision risk with orbital debris and radiation environment can be shown to be improved in lower altitude orbits, whilst compliance with IADC guidelines for spacecraft post-mission lifetime and deorbit is also assisted. Finally, VLEO offers opportunities to exploit novel atmosphere-breathing electric propulsion systems and aerodynamic attitude and orbit control methods. However, key challenges associated with our understanding of the lower thermosphere, aerodynamic drag, the requirement to provide a meaningful orbital lifetime whilst minimising spacecraft mass and complexity, and atomic oxygen erosion still require further research. Given the scope for significant commercial, societal, and environmental impact which can be realised with higher performing Earth observation platforms, renewed research efforts to address the challenges associated with VLEO operations are required

Concepts and Applications of Aerodynamic Attitude and Orbital Control for Spacecraft in Very Low Earth Orbit

Spacecraft operations below 450km, namely Very Low Earth Orbit (VLEO), can offer significant advantages over traditional low Earth orbits, for example enhanced ground resolution for Earth observation, improved communications latency and link budget, or improved signal-to-noise ratio. Recently, these lower orbits have begun to be exploited as a result of technology development, particularly component miniaturisation and cost-reduction, and concerns over the increasing debris population in commercially exploited orbits. However, the high cost of orbital launch and challenges associated with atmospheric drag, causing orbital decay and eventually re-entry are still a key barrier to their wider use for large commercial and civil spacecraft. Efforts to address the impact of aerodynamic drag are being sought through the development of novel drag-compensation propulsion systems and identification of materials which can reduce aerodynamic drag by specularly reflecting the incident gas. However, the presence of aerodynamic forces can also be utilised to augment or improve spacecraft operations at these very low altitudes by providing the capability to perform coarse pointing control and trim or internal momentum management for example. This paper presents concepts for the advantageous use of spacecraft aerodynamics developed as part of DISCOVERER, a Horizon 2020 funded project with the aim to revolutionise Earth observation satellite operations in VLEO. The combination of novel spacecraft geometries and use of aerodynamic control methods are explored, demonstrating the potential for a new generation of Earth observation satellites operating at lower altitudes

Discoverer - Making commercial satellite operations in very low earth orbit a reality

DISCOVERER is a €5.7M European Commission funded Horizon 2020 project developing technologies to enable commercially-viable sustained-operation of satellites in very low Earth orbits. Why operate closer to the Earth? For communications applications latency is significantly reduced and link budgets improved, and for remote sensing improved link budgets allow higher resolution or smaller instruments, all providing cost benefits. In addition, all applications benefit from increased launch mass to lower altitudes, whilst end-of-life removal is ensured due to the increased atmospheric drag. However, this drag must also be minimised and compensated for. One of the key technologies being developed by DISCOVERER are materials that encourage specular reflection of the residual atmosphere at these altitudes. Combined with appropriate geometric designs these can significantly reduce drag, provide usable lift for aerodynamic attitude and orbit control, and improve the collection efficiency of aerodynamic intakes for atmosphere breathing electric propulsion systems, all of which are being developed as part of DISCOVERER. The paper provides highlights from the developments to date, and the potential for a new class of aerodynamic commercial satellites operating at altitudes below the International Space Station

A review of gas-surface interaction models for orbital aerodynamics applications

Renewed interest in Very Low Earth Orbits (VLEO) - i.e. altitudes below 450 km - has led to an increased demand for accurate environment characterisation and aerodynamic force prediction. While the former requires knowledge of the mechanisms that drive density variations in the thermosphere, the latter also depends on the interactions between the gas-particles in the residual atmosphere and the surfaces exposed to the flow. The determination of the aerodynamic coefficients is hindered by the numerous uncertainties that characterise the physical processes occurring at the exposed surfaces. Several models have been produced over the last 60 years with the intent of combining accuracy with relatively simple implementations. In this paper the most popular models have been selected and reviewed using as discriminating factors relevance with regards to orbital aerodynamics applications and theoretical agreement with gas-beam experimental data. More sophisticated models were neglected, since their increased accuracy is generally accompanied by a substantial increase in computation times which is likely to be unsuitable for most space engineering applications. For the sake of clarity, a distinction was introduced between physical and scattering kernel theory based gas-surface interaction models. The physical model category comprises the Hard Cube model, the Soft Cube model and the Washboard model, while the scattering kernel family consists of the Maxwell model, the Nocilla-Hurlbut-Sherman model and the Cercignani-Lampis-Lord model. Limits and assets of each model have been discussed with regards to the context of this paper. Wherever possible, comments have been provided to help the reader to identify possible future challenges for gas-surface interaction science with regards to orbital aerodynamic applications

The structural basis for partitioning of the XRCC1/DNA ligase III-α BRCT-mediated dimer complexes

The ultimate step common to almost all DNA repair pathways is the ligation of the nicked intermediate to form contiguous double-stranded DNA. In the mammalian nucleotide and base excision repair pathways, the ligation step is carried out by ligase III-α. For efficient ligation, ligase III-α is constitutively bound to the scaffolding protein XRCC1 through interactions between the C-terminal BRCT domains of each protein. Although structural data for the individual domains has been available, no structure of the complex has been determined and several alternative proposals for this interaction have been advanced. Interpretation of the models is complicated by the formation of homodimers that, depending on the model, may either contribute to, or compete with heterodimer formation. We report here the structures of both homodimer complexes as well as the heterodimer complex. Structural characterization of the heterodimer formed from a longer XRCC1 BRCT domain construct, including residues comprising the interdomain linker region, revealed an expanded heterodimer interface with the ligase III-α BRCT domain. This enhanced linker-mediated binding interface plays a significant role in the determination of heterodimer/homodimer selectivity. These data provide fundamental insights into the structural basis of BRCT-mediated dimerization, and resolve questions related to the organization of this important repair complex

Attitude control for satellites flying in VLEO using aerodynamic surfaces

This paper analyses the use of aerodynamic control surfaces, whether passive or active, in order to carry out very low Earth orbit (VLEO) attitude maneuver operations. Flying a satellite in a very low Earth orbit with an altitude of less than 450 km, namely VLEO, is a technological challenge. It leads to several advantages, such as increasing the resolution of optical payloads or increase signal to noise ratio, among others. The atmospheric density in VLEO is much higher than in typical low earth orbit altitudes, but still free molecular flow. This has serious consequences for the maneuverability of a satellite because significant aerodynamic torques and forces are produced. In order to guarantee the controllability of the spacecraft they have to be analyzed in depth. Moreover, at VLEO the density of atomic oxygen increases, which enables the use of air-breathing electric propulsion (ABEP). Scientists are researching in this field to use ABEP as a drag compensation system, and consequently an attitude control based on aerodynamic control could make sense. This combination of technologies may represent an opportunity to open new markets. In this work, several satellite geometric configurations were considered to analyze aerodynamic control: 3-axis control with feather configuration and 2-axis control with shuttlecock configuration. The analysis was performed by simulating the attitude of the satellite as well as the disturbances affecting the spacecraft. The models implemented to simulate the disturbances were the following: Gravitational gradient torque disturbance, magnetic dipole torque disturbance (magnetic field model IGRF12), and aerodynamic torque disturbances (aerodynamic model DTM2013 and wind model HWM14).The maneuvers analyzed were the following: detumbling or attitude stabilization, pointing and demisability. Different VLEO parameters were analyzed for every geometric configuration and spacecraft maneuver. The results determined which of the analyzed geometric configurations suits better for every maneuver