Left High and Dry: Deglaciation of Dogger Bank, North Sea, Recorded in Proglacial Lake Evolution

Reconstructions of palaeo-ice sheet retreat in response to climate warming using offshore archives can provide vital analogs for future ice-sheet behavior. At the Last Glacial Maximum, Dogger Bank, in the southern North Sea, was covered by the Eurasian Ice Sheet. However, the maximum extent and behavior of the ice sheet in the North Sea basin is poorly constrained. We reveal ice-marginal dynamics and maximum ice extent at Dogger Bank through sedimentological and stratigraphic investigation of glacial and proglacial lake sediments. We use a large, integrated subsurface dataset of shallow seismic reflection and geotechnical data collected during windfarm site investigation. For the first time, an ice stream is identified at Dogger Bank, based on preserved subglacial bedforms, eskers and meltwater channels. During ice-sheet advance, a terminal thrust-block moraine complex formed, whose crest runs approximately north-northeast to south-southwest. Subsequent ice stream shutdown caused stagnation of ice, and rapid retreat of the ice-sheet margin. The moraine complex, and outwash head from an adjacent ice-sheet lobe to the west, dammed a large (approximately 750 km2) proglacial lake. Subsequent sedimentation infilled the lake with 30 m of glacial outwash sediments. A lobate subaqueous fan formed at the ice-sheet margin, which thins toward the southeast with iceberg scours and ice-rafted debris at the base, and is onlapped by lake sediments calibrated to core as alternating clay and silt laminae, interpreted to be varves. The lake became isolated from the retreating ice-sheet margin, and ice-sheet retreat slowed. Sediment-laden meltwater was supplied to the ice-distal proglacial lake for c. 1500–2000 years. Subsequent ice-sheet retreat off Dogger Bank was more rapid due to the negative subglacial slope. The stepped retreat of rapid downwasting, slow retreat, and a final rapid phase off Dogger Bank occurred after the LGM at around 27 ka and before formation of a ribbon lake, dated previously to 23 ka and approximately 60 m lower in elevation, formed to the north of Dogger Bank. The complicated stratigraphic architecture revealed through these data improves forecasting of ground conditions for turbine footings at Dogger Bank, an important step in the provision of clean, sustainable energy

Topographic and hydrodynamic controls on barrier retreat and preservation: An example from Dogger Bank, North Sea

Barrier retreat can occur due to in-place drowning, overstepping or rollover, depending on the interplay of controls such as sea-level rise, sediment supply, coastal hydrodynamic regime and topography. Offshore sedimentary archives of barriers active during rapid Holocene sea-level rise provide important records of marine transgression, which are vital analogues to support appropriate mitigation strategies for future coastal realignment under projected relative sea-level rise scenarios. This study analyses the sedimentary archive at Dogger Bank, which is a formerly-glaciated area in the North Sea. Dogger Bank experienced marine transgression due to Early Holocene rapid relative sea-level rise. An integrated dataset of vibrocores and high-resolution seismic reflection data permits a stratigraphic framework to be established, which reveals the buried coastal geomorphology of the southern Dogger Bank for the first time. A transgressive stratigraphy was identified, comprising a topographically complicated basal glacial and terrestrial succession, overlain by two phases of barrier and tidal mudflat deposition, prior to shallow marine sedimentation. Barrier phase A was a recurved barrier drowned in place, and discontinuously overstepped to barrier phase B, which experienced continuous overstepping. By linking barrier elevations to relative sea-level curves, the timing of each barrier phase was established. Both barrier phases retreated during periods of rapid sea-level rise with abundant sediment supply. Coastal hydrodynamics (increasing wave energy) and antecedent topography with spatially variable accommodation are suggested to be the main reason for differing retreat mechanisms, rather than the rate of sea-level rise. Antecedent coastal geomorphology plays a critical role in erosional and depositional patterns during transgression, and therefore on the timing, rate and location of marine inundation, which needs to be included in models that aim to forecast hazards in coastal areas

Job retention vocational rehabilitation for employed people with inflammatory arthritis: adaptations to the Workwell trial due to the impact of the COVID-19 pandemic

There are high levels of work disability, absenteeism (sick leave) and presenteeism (reduced productivity) amongst people with inflammatory arthritis. Workwell is a multi-centre, randomised controlled trial of job retention vocational rehabilitation for employed people with inflammatory arthritis. The trial tested the effectiveness and cost-effectiveness of the Workwell programme compared to receipt of written self-help information only. Both arms continued to receive usual care. In March 2020, due to the COVID-19 pandemic, the Workwell trial paused to recruitment and intervention delivery. To successfully re-start, protocol amendments were rapidly submitted and changes to existing trial procedures made. The Workwell protocol was adapted in response to both the practical issues likely faced by many clinical research studies active across NHS sites during the pandemic, but also additional trial-specific challenges. A key eligibility criterion for the trial required participants to be in paid work for at least 15 hours per week. However, UK national lockdowns led to a substantial proportion of the workforce suddenly being furloughed or unable to work, and many people with arthritis taking immunosuppressive medications were asked to shield. Thus, the number of eligible participants reduced. Those continuing to work were harder to: identify as hospital clinics moved to remote delivery; screen, consent and then treat as hospital research staff and clinical therapists were re-deployed. New recruitment and consent strategies were applied and, where sites had reduced capacity, responsibilities were absorbed by the trial management team. Remote intervention delivery and electronic data capture were also implemented. By rapidly adapting the Workwell protocol and procedures, the trial successfully reopened to recruitment in July 2020, only four months after trial pause. We were able to achieve recruitment figures above the pre-COVID target and maintain a high retention rate. In addition, we found many of the protocol changes beneficial, as these streamlined trial procedures, thus improving efficiency. It is likely that many strategies implemented in response to the pandemic may become standard practice in future research within trials of a similar design and methodology

Ice sheet and palaeoclimate controls on drainage network evolution: an example from Dogger Bank, North Sea

Submerged landscapes on continental shelves archive drainage networks formed during periods of sea-level lowstand. The evolution of these postglacial drainage networks also reveals how past climate changes affected the landscape. Ice-marginal and paraglacial drainage networks on low-relief topography are susceptible to reorganisation of water supply, forced by ice-marginal rearrangement, precipitation and temperature variations, and marine inundation. A rare geological archive of climate-driven landscape evolution during the transition from ice-marginal (ca. 23 ka) to a fully submerged marine environment (ca. 8 ka) is preserved at Dogger Bank, in the southern North Sea. In this study, our analysis of high-resolution seismic reflection and cone penetration test data reveal a channel network over a 1330 km2 area that incised glacial and proglacial lake-fill sediments. The channel network sits below coastal and shallow marine sediments and is therefore interpreted to represent a terrestrial drainage network. When mapped out, the channel form morphology reveals two distinct sets. The first set comprises two low-sinuosity, wide (>400 m) channels that contain macroforms of braid and side bars. These channels are interpreted to have originated as proglacial rivers, which drained the ice-sheet margin to the north. The second set of channels (75–200 m wide, with one larger, ∼400 m wide) has higher sinuosity and forms a subdendritic network of tributaries to the proglacial channels. The timing of channel formation lacks chronostratigraphic control. However, the proglacial rivers must have formed as the ice sheet was still on Dogger Bank, before 23 ka, to supply meltwater to the rivers. Ice-sheet retreat from Dogger Bank led to reorganisation of meltwater drainage and abandonment of the proglacial rivers. Palaeoclimate simulations show a cold and dry period at Dogger Bank between 23 and 17 ka. After 17 ka, precipitation increased, and drainage of precipitation formed the second set of channels. The second set of rivers remained active until marine transgression of Dogger Bank at ca. 8.5–8 ka. Overall, this study provides a detailed insight into the evolution of river networks across Dogger Bank and highlights the interplay between external (climate) and internal (local) forcings in drainage network evolution

Toward homochiral protocells in noncatalytic peptide systems

The activation-polymerization-epimerization-depolymerization (APED) model of Plasson et al. has recently been proposed as a mechanism for the evolution of homochirality on prebiotic Earth. The dynamics of the APED model in two-dimensional spatially-extended systems is investigated for various realistic reaction parameters. It is found that the APED system allows for the formation of isolated homochiral proto-domains surrounded by a racemate. A diffusive slowdown of the APED network such as induced through tidal motion or evaporating pools and lagoons leads to the stabilization of homochiral bounded structures as expected in the first self-assembled protocells.Comment: 10 pages, 5 figure

Genes Are Often Sheltered from the Global Histone Hyperacetylation Induced by HDAC Inhibitors

Histone deacetylase inhibitors (HDACi) are increasingly used as therapeutic agents, but the mechanisms by which they alter cell behaviour remain unclear. Here we use microarray expression analysis to show that only a small proportion of genes (∼9%) have altered transcript levels after treating HL60 cells with different HDACi (valproic acid, Trichostatin A, suberoylanilide hydroxamic acid). Different gene populations respond to each inhibitor, with as many genes down- as up-regulated. Surprisingly, HDACi rarely induced increased histone acetylation at gene promoters, with most genes examined showing minimal change, irrespective of whether genes were up- or down-regulated. Many genes seem to be sheltered from the global histone hyperacetyation induced by HDACi

TReatIng Urinary symptoms in Men in Primary Healthcare using non-pharmacological and non-surgical interventions (TRIUMPH) compared with usual care: Study protocol for a cluster randomised controlled trial

Background: Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. In men, the prevalence and severity of LUTS increases with age, with a significant impact on quality of life. The majority of men presenting with LUTS are managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as the initial treatment. However, the provision of conservative therapies in primary care is variable and can be time and resource limited. GPs require practical resources to enhance patient engagement with such interventions. TRIUMPH aims to determine whether a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for LUTS versus usual care.Methods/design: TRIUMPH is a two-arm, cluster randomised controlled trial (RCT) being conducted in 30 National Health Service (NHS) general practices in England. The TRIUMPH intervention comprises a standardised LUTS advice booklet developed for the trial with patient and healthcare professional (HCP) consultation. The booklet is delivered to patients by nurses/healthcare assistants following assessment of their urinary symptoms. Patients are directed to relevant sections of the booklet, providing the manualised element of the intervention. To encourage adherence, HCPs provide follow-up contacts over 12 weeks. Practices are randomised 1:1 to either deliver the TRIUMPH intervention or a usual care pathway. The patient-reported International Prostate Symptom Score (IPSS) at 12 months post consent is the primary outcome. Secondary outcomes include cost-effectiveness, patient-reported outcomes on LUTS, quality of life, and patient and HCP acceptability and experience of the intervention. Primary analyses will be conducted on an intention-to-treat basis.Discussion: It is unclear whether conservative therapies for male LUTS are effectively delivered in primary care using current approaches. This can lead to men being inappropriately referred to secondary care or experiencing persistent symptoms. Primary care, therefore, holds the key to effective treatment for these men. The TRIUMPH intervention, through its standardised and manualised approach, has been developed to support GP practices in delivering effective conservative care. This pragmatic, cluster RCT should provide robust evidence in a primary-care setting to inform future guidelines

Cryptic Diversity of African Tigerfish (Genus Hydrocynus) Reveals Palaeogeographic Signatures of Linked Neogene Geotectonic Events

The geobiotic history of landscapes can exhibit controls by tectonics over biotic evolution. This causal relationship positions ecologically specialized species as biotic indicators to decipher details of landscape evolution. Phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, including fishes, can reveal key events of drainage evolution, notably where geochronological resolution is insufficient. Where geochronological resolution is insufficient, phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, notably fishes, can reveal key events of drainage evolution. This study evaluates paleo-environmental causes of mitochondrial DNA (mtDNA) based phylogeographic records of tigerfishes, genus Hydrocynus, in order to reconstruct their evolutionary history in relation to landscape evolution across Africa. Strong geographical structuring in a cytochrome b (cyt-b) gene phylogeny confirms the established morphological diversity of Hydrocynus and reveals the existence of five previously unknown lineages, with Hydrocynus tanzaniae sister to a clade comprising three previously unknown lineages (Groups B, C and D) and H. vittatus. The dated phylogeny constrains the principal cladogenic events that have structured Hydrocynus diversity from the late Miocene to the Plio-Pleistocene (ca. 0–16 Ma). Phylogeographic tests reveal that the diversity and distribution of Hydrocynus reflects a complex history of vicariance and dispersals, whereby range expansions in particular species testify to changes to drainage basins. Principal divergence events in Hydrocynus have interfaced closely with evolving drainage systems across tropical Africa. Tigerfish evolution is attributed to dominant control by pulses of geotectonism across the African plate. Phylogenetic relationships and divergence estimates among the ten mtDNA lineages illustrates where and when local tectonic events modified Africa's Neogene drainage. Haplotypes shared amongst extant Hydrocynus populations across northern Africa testify to recent dispersals that were facilitated by late Neogene connections across the Nilo-Sahelian drainage. These events in tigerfish evolution concur broadly with available geological evidence and reveal prominent control by the African Rift System, evident in the formative events archived in phylogeographic records of tigerfish

Different Conformations of Phosphatase and Tensin Homolog, Deleted on Chromosome 10 (PTEN) Protein within the Nucleus and Cytoplasm of Neurons

PTEN is a critical gene involved in the regulation of many cellular processes. The product of this gene has dual phosphatase activity and is able to dephosphorylate the 5′ end of the phosphatidylinositol (3,4,5)-trisphosphate. Within the cellular nucleus, this protein has been associated with regulation of the expression of many genes, although the mechanism of this regulation remains unclear. In this paper, two specific oligonucleotide aptamers were developed and selected, using the SELEX procedure, according to their ability to detect the PTEN protein in different subcellular compartments of neurons. While one aptamer was able to detect PTEN in the nucleus, the other recognized PTEN in the cytoplasm. The recognition pattern of PTEN by both aptamers was confirmed using antibodies in western blots of the proteins purified from mouse cerebellar homogenates and subcellular fractions. Additionally, we demonstrated that the two aptamers recognized different epitopes of the target peptide. The results presented here could not be fully explained by the canonical phosphatase structure of PTEN, suggesting the existence of different conformations of phosphatase in the nucleus and the cytoplasm