Importin‐αs are essential adapter proteins that recruit cytoplasmic proteins destined for active nuclear import to the nuclear transport machinery. Cargo proteins interact with the importin‐α ...armadillo repeat domain via nuclear localization sequences (NLSs), short amino acids motifs enriched in Lys and Arg residues. Plant genomes typically encode several importin‐α paralogs that can have both specific and partially redundant functions. Although some cargos are preferentially imported by a distinct importin‐α it remains unknown how this specificity is generated and to what extent cargos compete for binding to nuclear transport receptors. Here we report that the effector protein HaRxL106 from the oomycete pathogen Hyaloperonospora arabidopsidis co‐opts the host cell's nuclear import machinery. We use HaRxL106 as a probe to determine redundant and specific functions of importin‐α paralogs from Arabidopsis thaliana. A crystal structure of the importin‐α3/MOS6 armadillo repeat domain suggests that five of the six Arabidopsis importin‐αs expressed in rosette leaves have an almost identical NLS‐binding site. Comparison of the importin‐α binding affinities of HaRxL106 and other cargos in vitro and in plant cells suggests that relatively small affinity differences in vitro affect the rate of transport complex formation in vivo. Our results suggest that cargo affinity for importin‐α, sequence variation at the importin‐α NLS‐binding sites and tissue‐specific expression levels of importin‐αs determine formation of cargo/importin‐α transport complexes in plant cells.
In both plants and animals, nucleotide-binding leucine-rich repeat (NLR) immune receptors play critical roles in pathogen recognition and activation of innate immunity. In plants, NLRs recognise ...pathogen-derived effector proteins and initiate effector-triggered immunity (ETI). However, the molecular mechanisms that link NLR-mediated effector recognition and downstream signalling are not fully understood. By exploiting the well-characterised tomato Prf/Pto NLR resistance complex, we identified the 14-3-3 proteins TFT1 and TFT3 as interacting partners of both the NLR complex and the protein kinase MAPKKKα. Moreover, we identified the helper NRC proteins (NLR-required for cell death) as integral components of the Prf /Pto NLR recognition complex. Notably our studies revealed that TFTs and NRCs interact with distinct modules of the NLR complex and, following effector recognition, dissociate facilitating downstream signalling. Thus, our data provide a mechanistic link between activation of immune receptors and initiation of downstream signalling cascades.
Dust-enshrouded, starbursting, submillimeter galaxies (SMGs) at z ≥ 3 have been proposed as progenitors of z ≥ 2 compact quiescent galaxies (cQGs). To test this connection, we present a detailed ...spatially resolved study of the stars, dust, and stellar mass in a sample of six submillimeter-bright starburst galaxies at z ∼ 4.5. The stellar UV emission probed by HST is extended and irregular and shows evidence of multiple components. Informed by HST, we deblend Spitzer/IRAC data at rest-frame optical, finding that the systems are undergoing minor mergers with a typical stellar mass ratio of 1:6.5. The FIR dust continuum emission traced by ALMA locates the bulk of star formation in extremely compact regions (median re = 0.70 0.29 kpc), and it is in all cases associated with the most massive component of the mergers (median ). We compare spatially resolved UV slope (β) maps with the FIR dust continuum to study the infrared excess (IRX = LIR/LUV)-β relation. The SMGs display systematically higher IRX values than expected from the nominal trend, demonstrating that the FIR and UV emissions are spatially disconnected. Finally, we show that the SMGs fall on the mass-size plane at smaller stellar masses and sizes than the cQGs at z = 2. Taking into account the expected evolution in stellar mass and size between z = 4.5 and z = 2 due to the ongoing starburst and mergers with minor companions, this is in agreement with a direct evolutionary connection between the two populations.
The National Center for Atmospheric Research Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIE‐GCM) is utilized to understand the role that upward propagating tides play in ...determining the zonal mean state of the ionosphere‐thermosphere system. A sensitivity assessment of the TIE‐GCM shows that TIE‐GCM solutions greatly depend on the lower boundary conditions. We also establish the veracity of our TIE‐GCM solutions within and above the dynamo region. To isolate the mean effects of tidal dissipation, differences between TIE‐GCM simulations with and without lower boundary tidal forcing as specified by the Climatological Tidal Model of the Thermosphere are investigated. Dissipation of the DW1, (diurnal westward propagating tide with zonal wave number 1), diurnal eastward propagating tide with zonal wave number 3, and SW2 (semidiurnal tide with zonal wave number 2) explains most of ∼10–30 m s−1 seasonal and latitudinal variability in zonal winds within the dynamo region, with SW2 playing a greater role than ascribed in previous studies. Tidal dissipation at low latitudes causes a 9% decrease (30% increase) in O (O2) number densities near the F2 layer peak, leading to at least a 9% decrease in peak electron density (NmF2) throughout the year. F2 layer peak height (hmF2) differences of ‐4 to 2 km at low latitudes are explained by variations in the field‐aligned plasma motion driven by meridional wind differences induced by tidal dissipation. Compositional effects are mainly driven by DW1 and SW2, which differs from previous interpretations of tidal‐driven composition changes by DW1 “tidal mixing” exclusively. We suggest that tides may produce a net transport of constituents in the thermosphere similar to the way that, e.g., gravity waves can drive net transport of sodium in the mesosphere.
Key Points
Tidal dissipation affects mean IT conditions
The primary responsible tidal components are DW1, SW2, and DE3
Possible relevance to origins of IT trends
Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using ...a common database with defined parameters.
Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field.
Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response CR: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration.
These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.
•Electrochemotherapy (ECT) is highly efficient in the treatment of cutaneous metastases.•ECT is efficient across tumour histologies.•ECT response is higher for smaller tumours.•Intravenous bleomycin was more efficient than intratumoural, in tumours more than 2 cm size.•Linear array electrodes were more efficient in tumours less than 3 cm size.
Temporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories ...suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gaze onsets as a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N = 55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners' role. 'Sender' gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). 'Receiver' gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver's brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the 'sender' but not the 'receiver' of the mutual gaze.
Alterations in the proteome of Arabidopsis (Arabidopsis thaliana) leaves during responses to challenge by Pseudomonas syringae pv tomato DC3000 were analyzed using two-dimensional gel ...electrophoresis. Protein changes characteristic of the establishment of disease, basal resistance, and resistance-gene-mediated resistance were examined by comparing responses to DC3000, a hrp mutant, and DC3000 expressing avrRpm1, respectively. The abundance of each protein identified was compared with that of selected transcripts obtained from comparable GeneChip experiments. We report changes in three subcellular fractions: total soluble protein, chloroplast enriched, and mitochondria enriched over four time points (1.5-6 h after inoculation). In total, 73 differential spots representing 52 unique proteins were successfully identified. Many of the changes in protein spot density occurred before significant transcriptional reprogramming was evident between treatments. The high proportion of proteins represented by more than one spot indicated that many of the changes to the proteome can be attributed to posttranscriptional modifications. Proteins found to show significant change after bacterial challenge are representative of two main functional groups: defense-related antioxidants and metabolic enzymes. Significant changes to photosystem II and to components of the mitochondrial permeability transition were also identified. Rapid communication between organelles and regulation of primary metabolism through redox-mediated signaling are supported by our data.
We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the ...burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1 × 1013 (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.
Plants use intracellular nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing immune receptors (NLRs) to detect pathogen-derived effector proteins. The
NLR pair RRS1-R/RPS4 ...confers disease resistance to different bacterial pathogens by perceiving the structurally distinct effectors AvrRps4 from
pv.
and PopP2 from
via an integrated WRKY domain in RRS1-R. How the WRKY domain of RRS1 (RRS1
) perceives distinct classes of effector to initiate an immune response is unknown. Here, we report the crystal structure of the in planta processed C-terminal domain of AvrRps4 (AvrRps4
) in complex with RRS1
Perception of AvrRps4
by RRS1
is mediated by the β2-β3 segment of RRS1
that binds an electronegative patch on the surface of AvrRps4
Structure-based mutations that disrupt AvrRps4
-RRS1
interactions in vitro compromise RRS1/RPS4-dependent immune responses. We also show that AvrRps4
can associate with the WRKY domain of the related but distinct RRS1B/RPS4B NLR pair, and the DNA-binding domain of
WRKY41, with similar binding affinities and how effector binding interferes with WRKY-W-box DNA interactions. This work demonstrates how integrated domains in plant NLRs can directly bind structurally distinct effectors to initiate immunity.
This study used questionnaires to examine the patient-reported satisfaction with 2 hearing implant devices to determine the level of overall satisfaction with the devices, which, if any, factors ...predicted good or poor perceived outcomes, or whether there were any specific aspects of the devices where dissatisfaction was apparent.
A post-treatment questionnaire survey of 39 adult patients who had received a Vibrant Soundbridge (VSB) or Bonebridge (BB) hearing implant, with at least 3 months of follow-up, was conducted using the Glasgow Benefit Inventory (GBI) and Hearing Device Satisfaction Scale (HDSS). Satisfaction scores were compared to pre- and post-operative audiologic outcomes. The correlation between GBI and HDSS scores was also examined.
A total of 28 of the 39 patients (72%) responded: 13 with a BB and 15 with a VSB at a mean of 13 months after implantation. The overall mean total GBI score was 30, with no significant differences across the groups. The responders generally reported that they were "satisfied" across most domains of the HDSS. In the study, 25 of the 28 responders were largely satisfied with their devices but 3 respondents were not. Two were known non-users, while one used the device but did not gain the benefit expected. It is instructive to note that all of these dissatisfied recipients were close to the manufacturer recommended limits for implantation of their respective devices at the time of surgery. Certain themes were identified within the patients' responses, indicating common aspects where satisfaction was poorer.
This series of 28 implant recipients demonstrates high levels of satisfaction with implantable hearing devices across 2 different validated questionnaires. Implant teams could exercise caution and manage patient expectations if the patients are close to the recommended limits of a particular device.
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