A prebiotic basis for ATP as the universal energy currency

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions

Optimising use of 4D-CT phase information for radiomics analysis in lung cancer patients treated with stereotactic body radiotherapy

From IOP Publishing via Jisc Publications RouterHistory: received 2021-03-17, oa-requested 2021-04-07, accepted 2021-04-21, epub 2021-05-24, open-access 2021-05-24, ppub 2021-06-07Publication status: PublishedFunder: Cancer Research UK; doi: https://doi.org/10.13039/501100000289; Grant(s): C147/A25254Abstract: Purpose. 4D-CT is routine imaging for lung cancer patients treated with stereotactic body radiotherapy. No studies have investigated optimal 4D phase selection for radiomics. We aim to determine how phase data should be used to identify prognostic biomarkers for distant failure, and test whether stability assessment is required. A phase selection approach will be developed to aid studies with different 4D protocols and account for patient differences. Methods. 186 features were extracted from the tumour and peritumour on all phases for 258 patients. Feature values were selected from phase features using four methods: (A) mean across phases, (B) median across phases, (C) 50% phase, and (D) the most stable phase (closest in value to two neighbours), coined personalised selection. Four levels of stability assessment were also analysed, with inclusion of: (1) all features, (2) stable features across all phases, (3) stable features across phase and neighbour phases, and (4) features averaged over neighbour phases. Clinical-radiomics models were built for twelve combinations of feature type and assessment method. Model performance was assessed by concordance index (c-index) and fraction of new information from radiomic features. Results. The most stable phase spanned the whole range but was most often near exhale. All radiomic signatures provided new information for distant failure prediction. The personalised model had the highest c-index (0.77), and 58% of new information was provided by radiomic features when no stability assessment was performed. Conclusion. The most stable phase varies per-patient and selecting this improves model performance compared to standard methods. We advise the single most stable phase should be determined by minimising feature differences to neighbour phases. Stability assessment over all phases decreases performance by excessively removing features. Instead, averaging of neighbour phases should be used when stability is of concern. The models suggest that higher peritumoural intensity predicts distant failure

Open-World Object Manipulation using Pre-trained Vision-Language Models

For robots to follow instructions from people, they must be able to connect the rich semantic information in human vocabulary, e.g. "can you get me the pink stuffed whale?" to their sensory observations and actions. This brings up a notably difficult challenge for robots: while robot learning approaches allow robots to learn many different behaviors from first-hand experience, it is impractical for robots to have first-hand experiences that span all of this semantic information. We would like a robot's policy to be able to perceive and pick up the pink stuffed whale, even if it has never seen any data interacting with a stuffed whale before. Fortunately, static data on the internet has vast semantic information, and this information is captured in pre-trained vision-language models. In this paper, we study whether we can interface robot policies with these pre-trained models, with the aim of allowing robots to complete instructions involving object categories that the robot has never seen first-hand. We develop a simple approach, which we call Manipulation of Open-World Objects (MOO), which leverages a pre-trained vision-language model to extract object-identifying information from the language command and image, and conditions the robot policy on the current image, the instruction, and the extracted object information. In a variety of experiments on a real mobile manipulator, we find that MOO generalizes zero-shot to a wide range of novel object categories and environments. In addition, we show how MOO generalizes to other, non-language-based input modalities to specify the object of interest such as finger pointing, and how it can be further extended to enable open-world navigation and manipulation. The project's website and evaluation videos can be found at https://robot-moo.github.io/Comment: Accepted at the 7th Conference on Robot Learning (CoRL 2023

The essential value of long-term experimental data for hydrology and water management

We would like to thank the European Research Council ERC for funding the VeWa project and most of Tetzlaff's time (project GA 335910 VeWa). No data were used in producing this manuscript.Peer reviewedPublisher PD

Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 ​mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits’ muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging

Rfam: updates to the RNA families database

Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/

Pfam: clans, web tools and services

Pfam is a database of protein families that currently contains 7973 entries (release 18.0). A recent development in Pfam has enabled the grouping of related families into clans. Pfam clans are described in detail, together with the new associated web pages. Improvements to the range of Pfam web tools and the first set of Pfam web services that allow programmatic access to the database and associated tools are also presented. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://pfam.cgb.ki.se/)

Improving weekend handover between junior doctors on medical and surgical wards.

Poor weekend handover has been implicated as one of the causes of observed higher mortality rates at weekends in UK hospitals. In a large teaching hospital we, a group of junior doctors, set about improving the quality and effectiveness of weekend handover. We used the Model for Improvement to implement a weekend handover sticker through an iterative process using multiple Plan/Do/Study/Act (PDSA) cycles. Over the 16 week study period the number of completed weekend tasks increased by 30% and the number of patients with a documented weekend handover increased by nearly 50%. Junior doctors are well positioned to notice the quality and safety shortcomings within hospitals, and by using effective improvement methods they can improve these systems at little or no cost.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.Published