Hydrodynamic insights into the paleobiology of the Ediacaran rangeomorph Fractofusus misrai.

The Ediacaran of Newfoundland preserves some of the oldest complex macroscopic communities, several of which are dominated by the fractal-like rangeomorph genus Fractofusus. Here we use computational fluid dynamics and a detailed reconstruction of Fractofusus misrai to document for the first time hydrodynamic phenomena associated with this sediment-reclining organism and its rangeomorph elements that are relevant to interpreting feeding strategies, explain the recently documented rheotropic growth oblique to currents, and provide insights into their impact on the Ediacaran seafloor. Obliquely oriented Fractofusus are common, likely representing a compromise between maximized aspect ratio and minimization of drag. Flow patterns on the upper surface of Fractofusus are consistent with the collection of dissolved and finely particulate nutrients, as well as gas exchange. Fractofusus produce a wake downstream, demonstrating that reclining rangeomorphs had potential to modify sedimentation patterns on the ancient seafloor by potentially allowing deposition of fine-grained sediment.

Earth's sinking surface.

China's major cities show considerable subsidence from human activities.

Disappearing cities on US coasts.

The sea level along the US coastlines is projected to rise by 0.25-0.3 m by 2050, increasing the probability of more destructive flooding and inundation in major cities1-3. However, these impacts may be exacerbated by coastal subsidence-the sinking of coastal land areas4-a factor that is often underrepresented in coastal-management policies and long-term urban planning2,5. In this study, we combine high-resolution vertical land motion (that is, raising or lowering of land) and elevation datasets with projections of sea-level rise to quantify the potential inundated areas in 32 major US coastal cities. Here we show that, even when considering the current coastal-defence structures, further land area of between 1,006 and 1,389 km2 is threatened by relative sea-level rise by 2050, posing a threat to a population of 55,000-273,000 people and 31,000-171,000 properties. Our analysis shows that not accounting for spatially variable land subsidence within the cities may lead to inaccurate projections of expected exposure. These potential consequences show the scale of the adaptation challenge, which is not appreciated in most US coastal cities.

Current trends in macromolecular model refinement and validation.

The Guest Editors provide an introduction to the special issue of articles based on talks at the CCP4 Study Weekend 2022, which is available at https://journals.iucr.org/special_issues/2023/CCP42022/.

Neutron crystallographic refinement with REFMAC5 from the CCP4 suite.

Hydrogen (H) atoms are abundant in macromolecules and often play critical roles in enzyme catalysis, ligand-recognition processes and protein-protein interactions. However, their direct visualization by diffraction techniques is challenging. Macromolecular X-ray crystallography affords the localization of only the most ordered H atoms at (sub-)atomic resolution (around 1.2 Šor higher). However, many H atoms of biochemical significance remain undetectable by this method. In contrast, neutron diffraction methods enable the visualization of most H atoms, typically in the form of deuterium (2H) atoms, at much more common resolution values (better than 2.5 Å). Thus, neutron crystallography, although technically demanding, is often the method of choice when direct information on protonation states is sought. REFMAC5 from the Collaborative Computational Project No. 4 (CCP4) is a program for the refinement of macromolecular models against X-ray crystallographic and cryo-EM data. This contribution describes its extension to include the refinement of structural models obtained from neutron crystallographic data. Stereochemical restraints with accurate bond distances between H atoms and their parent atom nuclei are now part of the CCP4 Monomer Library, the source of prior chemical information used in the refinement. One new feature for neutron data analysis in REFMAC5 is refinement of the protium/deuterium (1H/2H) fraction. This parameter describes the relative 1H/2H contribution to neutron scattering for hydrogen isotopes. The newly developed REFMAC5 algorithms were tested by performing the (re-)refinement of several entries available in the PDB and of one novel structure (FutA) using either (i) neutron data only or (ii) neutron data supplemented by external restraints to a reference X-ray crystallographic structure. Re-refinement with REFMAC5 afforded models characterized by R-factor values that are consistent with, and in some cases better than, the originally deposited values. The use of external reference structure restraints during refinement has been observed to be a valuable strategy, especially for structures at medium-low resolution.

Exploratory modelling of the impacts of sea-level rise on the Sundarbans mangrove forest, West Bengal, India.

In this paper we conduct exploratory simulations of the possible evolution of the Indian Sundarbans mangroves to 2100 under a range of future sea-level rise (SLR) scenarios, considering the effects of both inundation and shoreline erosion. The Sea Level Affecting Marshes Model (SLAMM) is used to simulate habitat transitions due to inundation and these outputs are combined with an empirical model of SLR-driven shoreline erosion. A set of plausible climate-induced SLR scenarios are considered, together with delta subsidence and constrained vertical sediment accretion. Significant mangrove decline is found in all cases: the greater the rise in sea level the greater the losses. By the end of the century, the Indian Sundarbans mangroves could lose between 42 % and 80 % of their current area if current management is continued. Managed realignment could offset these losses but at the expense of productive land and the migration of the human population.

GEMMI and Servalcat restrain REFMAC5.

Macromolecular refinement uses experimental data together with prior chemical knowledge (usually digested into geometrical restraints) to optimally fit an atomic structural model into experimental data, while ensuring that the model is chemically plausible. In the CCP4 suite this chemical knowledge is stored in a Monomer Library, which comprises a set of restraint dictionaries. To use restraints in refinement, the model is analysed and template restraints from the dictionary are used to infer (i) restraints between concrete atoms and (ii) the positions of riding hydrogen atoms. Recently, this mundane process has been overhauled. This was also an opportunity to enhance the Monomer Library with new features, resulting in a small improvement in REFMAC5 refinement. Importantly, the overhaul of this part of CCP4 has increased flexibility and eased experimentation, opening up new possibilities.

Insulin secretion deficits in a Prader-Willi syndrome ß-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.

Prader-Willi syndrome (PWS) is a multisystem disorder with neurobehavioral, metabolic, and hormonal phenotypes, caused by loss of expression of a paternally-expressed imprinted gene cluster. Prior evidence from a PWS mouse model identified abnormal pancreatic islet development with retention of aged insulin and deficient insulin secretion. To determine the collective roles of PWS genes in ß-cell biology, we used genome-editing to generate isogenic, clonal INS-1 insulinoma lines having 3.16 Mb deletions of the silent, maternal- (control) and active, paternal-allele (PWS). PWS ß-cells demonstrated a significant cell autonomous reduction in basal and glucose-stimulated insulin secretion. Further, proteomic analyses revealed reduced levels of cellular and secreted hormones, including all insulin peptides and amylin, concomitant with reduction of at least ten endoplasmic reticulum (ER) chaperones, including GRP78 and GRP94. Critically, differentially expressed genes identified by whole transcriptome studies included reductions in levels of mRNAs encoding these secreted peptides and the group of ER chaperones. In contrast to the dosage compensation previously seen for ER chaperones in Grp78 or Grp94 gene knockouts or knockdown, compensation is precluded by the stress-independent deficiency of ER chaperones in PWS ß-cells. Consistent with reduced ER chaperones levels, PWS INS-1 ß-cells are more sensitive to ER stress, leading to earlier activation of all three arms of the unfolded protein response. Combined, the findings suggest that a chronic shortage of ER chaperones in PWS ß-cells leads to a deficiency of protein folding and/or delay in ER transit of insulin and other cargo. In summary, our results illuminate the pathophysiological basis of pancreatic ß-cell hormone deficits in PWS, with evolutionary implications for the multigenic PWS-domain, and indicate that PWS-imprinted genes coordinate concerted regulation of ER chaperone biosynthesis and ß-cell secretory pathway function.

Global survey shows planners use widely varying sea-level rise projections for coastal adaptation.

Including sea-level rise (SLR) projections in planning and implementing coastal adaptation is crucial. Here we analyze the first global survey on the use of SLR projections for 2050 and 2100. Two-hundred and fifty-three coastal practitioners engaged in adaptation/planning from 49 countries provided complete answers to the survey which was distributed in nine languages - Arabic, Chinese, English, French, Hebrew, Japanese, Korean, Portuguese and Spanish. While recognition of the threat of SLR is almost universal, only 72% of respondents currently utilize SLR projections. Generally, developing countries have lower levels of utilization. There is no global standard in the use of SLR projections: for locations using a standard data structure, 53% are planning using a single projection, while the remainder are using multiple projections, with 13% considering a low-probability high-end scenario. Countries with histories of adaptation and consistent national support show greater assimilation of SLR projections into adaptation decisions. This research provides new insights about current planning practices and can inform important ongoing efforts on the application of the science that is essential to the promotion of effective adaptation.

Benefits of subsidence control for coastal flooding in China.

Land subsidence is impacting large populations in coastal Asia via relative sea-level rise (RSLR). Here we assesses these risks and possible response strategies for China, including estimates of present rates of RSLR, flood exposure and risk to 2050. In 2015, each Chinese coastal resident experienced on average RSLR of 11 to 20 mm/yr. This is 3 to 5 times higher than climate-induced SLR, reflecting that people are concentrated in subsiding locations. In 2050, assuming these subsidence rates continue, land area, population and assets exposed to the 100-year coastal flood event is 20%-39%, 17%-37% and 18%-39% higher than assuming climate change alone, respectively. Realistic subsidence control measures can avoid up to two thirds of this additional growth in exposure, with adaptation required to address the residual. This analysis emphasizes subsidence as a RSLR hazard in China that requires a broad-scale policy response, utilizing subsidence control combined with coastal adaptation.

CCP4 Cloud for structure determination and project management in macromolecular crystallography.

Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at the cost of increasing data volumes. This is due to the deployment of modern high-speed, high-resolution detectors, the increased complexity and variety of crystallographic software, the use of extensive databases and high-performance computing. This limits what can be accomplished with personal, offline, computing equipment in terms of both productivity and maintainability. There is also an issue of long-term data maintenance and availability of structure-solution projects as the links between experimental observations and the final results deposited in the PDB. In this article, CCP4 Cloud, a new front-end of the CCP4 software suite, is presented which mitigates these effects by providing an online, cloud-based environment for crystallographic computation. CCP4 Cloud was developed for the efficient delivery of computing power, database services and seamless integration with web resources. It provides a rich graphical user interface that allows project sharing and long-term storage for structure-solution projects, and can be linked to data-producing facilities. The system is distributed with the CCP4 software suite version 7.1 and higher, and an online publicly available instance of CCP4 Cloud is provided by CCP4.

Targeting climate adaptation to safeguard and advance the Sustainable Development Goals.

The international community has committed to achieve 169 Sustainable Development Goal (SDG) targets by 2030 and to enhance climate adaptation under the Paris Agreement. Despite the potential for synergies, aligning SDG and climate adaptation efforts is inhibited by an inadequate understanding of the complex relationship between SDG targets and adaptation to impacts of climate change. Here we propose a framework to conceptualise how ecosystems and socio-economic sectors mediate this relationship, which provides a more nuanced understanding of the impacts of climate change on all 169 SDG targets. Global application of the framework reveals that adaptation of wetlands, rivers, cropland, construction, water, electricity, and housing in the most vulnerable countries is required to safeguard achievement of 68% of SDG targets from near-term climate risk by 2030. We discuss how our framework can help align National Adaptation Plans with SDG targets, thus ensuring that adaptation advances, rather than detracts from, sustainable development.

Updated restraint dictionaries for carbohydrates in the pyranose form.

Restraint dictionaries are used during macromolecular structure refinement to encapsulate intramolecular connectivity and geometric information. These dictionaries allow previously determined `ideal' values of features such as bond lengths, angles and torsions to be used as restraint targets. During refinement, restraints influence the model to adopt a conformation that agrees with prior observation. This is especially important when refining crystal structures of glycosylated proteins, as their resolutions tend to be worse than those of nonglycosylated proteins. Pyranosides, the overwhelming majority component in all forms of protein glycosylation, often display conformational errors in crystal structures. Whilst many of these flaws usually relate to model building, refinement issues may also have their root in suboptimal restraint dictionaries. In order to avoid subsequent misinterpretation and to improve the quality of all pyranose monosaccharide entries in the CCP4 Monomer Library, new dictionaries with improved ring torsion restraints, coordinates reflecting the lowest-energy ring pucker and updated geometry have been produced and evaluated. These new dictionaries are now part of the CCP4 Monomer Library and will be released with CCP4 version 8.0.

Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase.

Human serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a 'closed' hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the α-phosphate of ATP. In contrast, in 'open' hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzyme-fragment structures show Tyr121 flipped out of its pocket in the core of the small domain. Data suggest that this ligandable pocket could be targeted by molecules that inhibit enzyme activity.

Sustainability of the coastal zone of the Ganges-Brahmaputra-Meghna delta under climatic and anthropogenic stresses.

The Ganges-Brahmaputra-Meghna (GBM) delta is one of the world's largest deltas. It is currently experiencing high rates of relative sea-level rise of about 5 mm/year, reflecting anthropogenic climate change and land subsidence. This is expected to accelerate further through the 21st Century, so there are concerns that the GBM delta will be progressively submerged. In this context, a core question is: can sedimentation on the delta surface maintain its elevation relative to sea level? This research seeks to answer this question by applying a two-dimensional flow and morphological model which is capable of handling dynamic interactions between the river and floodplain systems and simulating floodplain sedimentation under different flow-sediment regimes and anthropogenic interventions. We find that across a range of flood frequencies and adaptation scenarios (including the natural polder-free state), the retained volume of sediment varies between 22% and 50% of the corresponding sediment input. This translates to average rates of sedimentation on the delta surface of 5.5 mm/yr to 7.5 mm/yr. Hence, under present conditions, sedimentation associated with quasi-natural conditions can exceed current rates of relative sea-level rise and potentially create new land mass. These findings highlight that encouraging quasi-natural conditions through the widespread application of active sediment management measures has the potential to promote more sustainable outcomes for the GBM delta. Practical measures to promote include tidal river management, and appropriate combinations of cross-dams, bandal-like structures, and dredging.

Developing socio-ecological scenarios: A participatory process for engaging stakeholders.

Deltas are experiencing profound demographic, economic and land use changes and human-induced catchment and climate change. Bangladesh exemplifies these difficulties through multiple climate risks including subsidence/sea-level rise, temperature rise, and changing precipitation patterns, as well as changing management of the Ganges and Brahmaputra catchments. There is a growing population and economy driving numerous more local changes, while dense rural population and poverty remain significant. Identifying appropriate policy and planning responses is extremely difficult in these circumstances. This paper adopts a participatory scenario development process incorporating both socio-economic and biophysical elements across multiple scales and sectors as part of an integrated assessment of ecosystem services and livelihoods in coastal Bangladesh. Rather than simply downscale global perspectives, the analysis was driven by a large and diverse stakeholder group who met with the researchers over four years as the assessment was designed, implemented and applied. There were four main stages: (A) establish meta-framework for the analysis; (B) develop qualitative scenarios of key trends; (C) translate these scenarios into quantitative form for the integrated assessment model analysis; and (D) a review of the model results, which raises new stakeholder insights (e.g., preferred adaptation and policy responses) and questions. Step D can be repeated leading to an iterative learning loop cycle, and the process can potentially be ongoing. The strong and structured process of stakeholder engagement gave strong local ownership of the scenarios and the wider process. This process can be generalised for widespread application across socio-ecological systems following the same four-stage approach. It demands sustained engagement with stakeholders and hence needs to be linked to a long-term research process. However, it facilitates a more credible foundation for planning especially where there are multiple interacting factors.

Towards Consistency in Geometry Restraints for Carbohydrates in the Pyranose form: Modern Dictionary Generators Reviewed.

Macromolecular restrained refinement is nowadays the most used method for improving the agreement between an atomic structural model and experimental data. Restraint dictionaries, a key tool behind the success of the method, allow fine-tuning geometric properties such as distances and angles between atoms beyond simplistic expectations. Dictionary generators can provide restraint target estimates derived from different sources, from fully theoretical to experimental and any combination in between. Carbohydrates are stereochemically complex biomolecules and, in their pyranose form, have clear conformational preferences. As such, they pose unique problems to dictionary generators and in the course of this study, require special attention from software developers. Functional differences between restraint generators will be discussed, as well as the process of achieving consistent results with different software designs. The study will conclude a set of practical considerations, as well as recommendations for the generation of new restraint dictionaries, using the improved software alternatives discussed.

Twenty-first-century projections of shoreline change along inlet-interrupted coastlines.

Sandy coastlines adjacent to tidal inlets are highly dynamic and widespread landforms, where large changes are expected due to climatic and anthropogenic influences. To adequately assess these important changes, both oceanic (e.g., sea-level rise) and terrestrial (e.g., fluvial sediment supply) processes that govern the local sediment budget must be considered. Here, we present novel projections of shoreline change adjacent to 41 tidal inlets around the world, using a probabilistic, reduced complexity, system-based model that considers catchment-estuary-coastal systems in a holistic way. Under the RCP 8.5 scenario, retreat dominates (90% of cases) over the twenty-first century, with projections exceeding 100 m of retreat in two-thirds of cases. However, the remaining systems are projected to accrete under the same scenario, reflecting fluvial influence. This diverse range of response compared to earlier methods implies that erosion hazards at inlet-interrupted coasts have been inadequately characterised to date. The methods used here need to be applied widely to support evidence-based coastal adaptation.

The missing link: covalent linkages in structural models.

Covalent linkages between constituent blocks of macromolecules and ligands have been subject to inconsistent treatment during the model-building, refinement and deposition process. This may stem from a number of sources, including difficulties with initially detecting the covalent linkage, identifying the correct chemistry, obtaining an appropriate restraint dictionary and ensuring its correct application. The analysis presented herein assesses the extent of problems involving covalent linkages in the Protein Data Bank (PDB). Not only will this facilitate the remediation of existing models, but also, more importantly, it will inform and thus improve the quality of future linkages. By considering linkages of known type in the CCP4 Monomer Library (CCP4-ML), failure to model a covalent linkage is identified to result in inaccurate (systematically longer) interatomic distances. Scanning the PDB for proximal atom pairs that do not have a corresponding type in the CCP4-ML reveals a large number of commonly occurring types of unannotated potential linkages; in general, these may or may not be covalently linked. Manual consideration of the most commonly occurring cases identifies a number of genuine classes of covalent linkages. The recent expansion of the CCP4-ML is discussed, which has involved the addition of over 16 000 and the replacement of over 11 000 component dictionaries using AceDRG. As part of this effort, the CCP4-ML has also been extended using AceDRG link dictionaries for the aforementioned linkage types identified in this analysis. This will facilitate the identification of such linkage types in future modelling efforts, whilst concurrently easing the process involved in their application. The need for a universal standard for maintaining link records corresponding to covalent linkages, and references to the associated dictionaries used during modelling and refinement, following deposition to the PDB is emphasized. The importance of correctly modelling covalent linkages is demonstrated using a case study, which involves the covalent linkage of an inhibitor to the main protease in various viral species, including SARS-CoV-2. This example demonstrates the importance of properly modelling covalent linkages using a comprehensive restraint dictionary, as opposed to just using a single interatomic distance restraint or failing to model the covalent linkage at all.