Using Shuttle Radar Topography to map ancient water channels in Mesopotamia

The Shuttle Radar Topography Mission (SRTM) is currently producing a digital elevation model of most of the world's surface. Here the authors assess its value in mapping and sequencing the network of water channels that provided the arterial system for Mesopotamia before the petrol engine

A national survey of current rehabilitation service provisions for people living with chronic kidney disease in the UK: Implications for policy and practice

Background: National guidance recognises the key role of rehabilitation in improving outcomes for people living with chronic kidney disease. Implementation of this guidance is reliant upon an adequate and skilled rehabilitation workforce. Data relating to this is currently lacking within the UK. This survey aimed to identify variations and good practices in kidney physiotherapy (PT), occupational therapy (OT) and clinical exercise physiologist (CEP) provision; and to understand barriers to implementation. Methods: An online survey was sent to all 87 UK kidney units between June 2022 and January 2023. Data was collected on the provision of therapy services, barriers to service provision and responses to the COVID-19 pandemic. The quantitative survey was analysed using descriptive statistics. Free-text responses were explored using reflexive thematic analysis. Results: Forty-five units (52%) responded. Seventeen (38%) units reported having a PT and 15 (33%) an OT with a specialist kidney role; one unit (7%) had access to a CEP. Thirty units (67%) offered inpatient therapy services, ten (22%) outpatient therapy clinics, six (13%) intradialytic exercise, six (13%) symptom management and three (7%) outpatient rehabilitation. Qualitative data revealed lack of money/funding and time (both n = 35, 85% and n = 34, 83% respectively) were the main barriers to delivering kidney-specific therapy. Responders saw an increase in the complexity of their caseload, a reduction in staffing levels and consequently, service provision during the COVID-19 pandemic. Exemplars of innovative service delivery, including hybrid digital and remote services, were viewed as positive responses to the COVID-19 pandemic. Conclusion: Despite clear evidence of the benefits of rehabilitation, across the UK, there remains limited and variable access to kidney-specific therapy services. Equitable access to kidney-specific rehabilitation services is urgently required to support people to ‘live well’ with kidney disease

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

yesMultiple pathways participate in the AMPA receptor trafficking that underlies long-term potentiation (LTP) of synaptic transmission. Here we demonstrate that protein SUMOylation is required for insertion of the GluA1 AMPAR subunit following transient glycine-evoked increase in AMPA receptor surface expression (ChemLTP) in dispersed neuronal cultures. ChemLTP increases co-localisation of SUMO-1 and the SUMO conjugating enzyme Ubc9 and with PSD95 consistent with the recruitment of SUMOylated proteins to dendritic spines. In addition, we show that ChemLTP increases dendritic levels of SUMO-1 and Ubc9 mRNA. Consistent with activity dependent translocation of these mRNAs to sites near synapses, levels of the mRNA binding and dendritic transport protein CPEB are also increased by ChemLTP. Importantly, reducing the extent of substrate protein SUMOylation by overexpressing the deSUMOylating enzyme SENP-1 or inhibiting SUMOylation by expressing dominant negative Ubc9 prevent the ChemLTP-induced increase in both AMPAR surface expression and dendritic SUMO-1 mRNA. Taken together these data demonstrate that SUMOylation of synaptic protein(s) involved in AMPA receptor trafficking is necessary for activity-dependent increases in AMPAR surface expression.Medical Research Council, the European Research Council and the Wellcome Trus

Spatial Stability of Incompressible Attachment-Line Flow

Linear stability analysis of incompressible attachment-line flow is presented within the spatial framework. The system of perturbation equations is solved using spectral collocation. This system has been solved in the past using the temporal approach and the current results are shown to be in excellent agreement with neutral temporal calculations. Results amenable to direct comparison with experiments are then presented for the case of zero suction. The global solution method utilized for solving the eigenproblem yields, aside from the well-understood primary mode, the full spectrum of least-damped waves. Of those, a new mode, well separated from the continuous spectrum is singled out and discussed. Further, relaxation of the condition of decaying perturbations in the far-field results in the appearance of sinusoidal modes akin to those found in the classical Orr-Sommerfeld problem. Finally, the continuous spectrum is demonstrated to be amenable to asymptotic analysis. Expressions are derived for the location, in parameter space, of the continuous spectrum, as well as for the limiting cases of practical interest. In the large Reynolds number limit the continuous spectrum is demonstrated to be identical to that of the Orr-Sommerfeld equation

Endothelial cells form transient Notch-dependent NO-containing cystic structures during zebrafish cerebrovascular development

Endothelial cell behaviour during blood vessel formation is highly complex and dynamic. Transgenic zebrafish have provided many new insights into these processes, due to their ability to provide detailed in vivo imaging. We here report a previously undescribed endothelial cell behaviour during zebrafish embryonic development. Endothelial cells of the cerebral vessels of 3-5d post fertilisation embryos extruded large membranous spherical structures. These were only found on the cerebral vessels, and did not detach from the parent vessel, instead regressing back into the endothelial cell. These structures did not communicate with the vessel lumen, exhibited periodic oscillations in size and shape, and were enriched with filamentous actin at their neck. Due to their unknown nature and spherical appearance we termed these structures kugeln (German for sphere). Pharmacological inhibition of vascular endothelial growth factor (VEGF) signalling significantly increased kugel number while Notch inhibition significantly reduced both kugel number and diameter. Kugeln contain little cytoplasm, but are highly positive for nitric oxide (NO) reactivity, suggesting they represent a novel NO containing organelle specific to the cerebral vessels

Asymmetric Hapln1a drives regionalized cardiac ECM expansion and promotes heart morphogenesis in zebrafish development

Aims Vertebrate heart development requires the complex morphogenesis of a linear tube to form the mature organ, a process essential for correct cardiac form and function, requiring coordination of embryonic laterality, cardiac growth, and regionalized cellular changes. While previous studies have demonstrated broad requirements for extracellular matrix (ECM) components in cardiac morphogenesis, we hypothesized that ECM regionalization may fine tune cardiac shape during heart development. Methods and results Using live in vivo light sheet imaging of zebrafish embryos, we describe a left-sided expansion of the ECM between the myocardium and endocardium prior to the onset of heart looping and chamber ballooning. Analysis using an ECM sensor revealed the cardiac ECM is further regionalized along the atrioventricular axis. Spatial transcriptomic analysis of gene expression in the heart tube identified candidate genes that may drive ECM expansion. This approach identified regionalized expression of hapln1a, encoding an ECM cross-linking protein. Validation of transcriptomic data by in situ hybridization confirmed regionalized hapln1a expression in the heart, with highest levels of expression in the future atrium and on the left side of the tube, overlapping with the observed ECM expansion. Analysis of CRISPR-Cas9-generated hapln1a mutants revealed a reduction in atrial size and reduced chamber ballooning. Loss-of-function analysis demonstrated that ECM expansion is dependent upon Hapln1a, together supporting a role for Hapln1a in regionalized ECM modulation and cardiac morphogenesis. Analysis of hapln1a expression in zebrafish mutants with randomized or absent embryonic left–right asymmetry revealed that laterality cues position hapln1a-expressing cells asymmetrically in the left side of the heart tube. Conclusion We identify a regionalized ECM expansion in the heart tube which promotes correct heart development, and propose a novel model whereby embryonic laterality cues orient the axis of ECM asymmetry in the heart, suggesting these two pathways interact to promote robust cardiac morphogenesis

Dual control of fault intersections on stop-start rupture in the 2016 Central Italy seismic sequence

Large continental earthquakes necessarily involve failure of multiple faults or segments. But these same critically-stressed systems sometimes fail in drawn-out sequences of smaller earthquakes over days or years instead. These two modes of failure have vastly different implications for seismic hazard and it is not known why fault systems sometimes fail in one mode or the other, or what controls the termination and reinitiation of slip in protracted seismic sequences. A paucity of modern observations of seismic sequences has hampered our understanding to-date, but a series of three Mw>6 earthquakes from August to November 2016 in Central Italy represents a uniquely well-observed example. Here we exploit a wealth of geodetic, seismological and field data to understand the spatio-temporal evolution of the sequence. Our results suggest that pre-existing fault structures controlled the extent and termination of rupture in each event in the sequence, and that fluid diffusion, channelled along these same structures, may have also determined the timing of rupture reinitiation. This dual control of subsurface structure on the stop-start rupture in seismic sequences may be common; future efforts should focus on investigating its prevalence