Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

The high-speed X-ray camera on AXIS

AXIS is a Probe-class mission concept that will provide high-throughput, high-spatial-resolution X-ray spectral imaging, enabling transformative studies of high-energy astrophysical phenomena. To take advantage of the advanced optics and avoid photon pile-up, the AXIS focal plane requires detectors with readout rates at least 20 times faster than previous soft X-ray imaging spectrometers flying aboard missions such as Chandra and Suzaku, while retaining the low noise, excellent spectral performance, and low power requirements of those instruments. We present the design of the AXIS high-speed X-ray camera, which baselines large-format MIT Lincoln Laboratory CCDs employing low-noise pJFET output amplifiers and a single-layer polysilicon gate structure that allows fast, low-power clocking. These detectors are combined with an integrated high-speed, low-noise ASIC readout chip from Stanford University that provides better performance than conventional discrete solutions at a fraction of their power consumption and footprint. Our complementary front-end electronics concept employs state of the art digital video waveform capture and advanced signal processing to deliver low noise at high speed. We review the current performance of this technology, highlighting recent improvements on prototype devices that achieve excellent noise characteristics at the required readout rate. We present measurements of the CCD spectral response across the AXIS energy band, augmenting lab measurements with detector simulations that help us understand sources of charge loss and evaluate the quality of the CCD backside passivation technique. We show that our technology is on a path that will meet our requirements and enable AXIS to achieve world-class science.Comment: 17 pages, 11 figures, submitted to Proceedings of SPIE Optics + Photonics 202

Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort

The GenOSept project was supported by the European Critical Care Research network and the European Society of Intensive Care Medicin

The salmon louse genome: Copepod features and parasitic adaptations

Copepods encompass numerous ecological roles including parasites, detrivores and phytoplankton grazers. Nonetheless, copepod genome assemblies remain scarce. Lepeophtheirus salmonis is an economically and ecologically important ectoparasitic copepod found on salmonid fish. We present the 695.4 Mbp L. salmonis genome assembly containing ≈60% repetitive regions and 13,081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics supported annotation and indicated a marked shift in gene expression after host attachment, including apparent downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of genes needed for peroxisome biogenesis, presence of numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite repeated development of resistance against chemical treatments L. salmonis exhibits low numbers of many genes involved in detoxification.publishedVersio

How binding of small molecule and peptide ligands to HIV-1 TAR alters the RNA motional landscape

The HIV-1 TAR RNA represents a well-known paradigm to study the role of dynamics and conformational change in RNA function. This regulatory RNA changes conformation in response to binding of Tat protein and of a variety of peptidic and small molecule ligands, indicating that its conformational flexibility and intrinsic dynamics play important roles in molecular recognition. We have used 13C NMR relaxation experiments to examine changes in the motional landscape of HIV-1 TAR in the presence of three ligands of different affinity and specificity. The ligands are argininamide, a linear peptide mimic of the Tat basic domain and a cyclic peptide that potently inhibits Tat-dependent activation of transcription. All three molecules induce the same motional characteristics within the three nucleotides bulge that represents the Tat-binding site. However, the cyclic peptide has a unique motional signature in the apical loop, which represents a binding site for the essential host co-factor cyclin T1. These results suggest that all peptidic mimics of Tat induce the same dynamics in TAR within this protein binding site. However, the new cyclic peptide mimic of Tat represents a new class of ligands with a unique effect on the dynamics and the structure of the apical loop

Uncertainty and Narratives of the Future. A Theoretical Framework for Contemporary Fertility

Explanations for fertility decisions based on structural constraints—such as labor, housing condition, or income—do not account for the contemporary fertility downturn faced by many countries in Europe. In this paper, we posit that the rise of uncertainty is central for understanding contemporary fertility dynamics. We propose a theoretical framework (the Narrative Framework) for the study of fertility decisions under uncertain conditions based on expectations, imaginaries and narratives. Relying on the idea of future–oriented action, we argue that uncertainty needs to be conceptualized and operationalized taking into account that people use works of imagination, producing their own narrative of the future. Narratives of the future are potent driving forces helping people to act according to or despite uncertainty. We present the different elements of the Narrative Framework and address its causal validity. We conclude by highlighting the advantages of taking into account the narratives of the future in fertility research