A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K(+)) channels and resultant K(+) efflux. Sperm-specific SLO3 K(+) channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K(+) conductance is both Ca(2+)- and pH i -sensitive. It has been debated whether Ca(2+)-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca(2+) sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca(2+) and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca(2+), the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca(2+) sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.info:eu-repo/semantics/publishe

Continent-Ocean Transition or Boundary? : Crowd-sourced seismic interpretations of the East-India Passive Margin

AcknowledgmentsThe authors would like to thank the full SEISMIX 2016 organization team and participants for facilitating and taking part in the experiment in Aviemore (Scotland). ION is thanked for supplying the seismic profile used in the experiments. Dr. Eagles and Dr. Pérez-Díaz are thanked for kindly sharing the interpretations of the E-India margin. JA is funded by “Juan de la Cierva-Incorporación” fellow-ship IJC2018-036074-I and “Ramón y Cajal” fellowship RYC2021-033872-I, funded by MCIN/AEI/https://doi.org/10.13039/501100011033 and the European Union NextGenerationEU/PRTR. We thank the reviewers for their constructive comments, and Jonathan Aitchison for the editorial guidance.Peer reviewedPostprintPublisher PD

Estimating Lorenz’s Reference State in an Ocean with a Nonlinear Equation of State for Seawater

The study of the mechanical energy budget of the oceans using the Lorenz available potential energy (APE) theory is based on knowledge of the adiabatically rearranged Lorenz reference state of minimum potential energy. The compressible and nonlinear character of the equation of state for seawater has been thought to cause the reference state to be ill defined, casting doubt on the usefulness of APE theory for investigating ocean energetics under realistic conditions. Using a method based on the volume frequency distribution of parcels as a function of temperature and salinity in the context of the seawater Boussinesq approximation, which is illustrated using climatological data, the authors show that compressibility effects are in fact minor. The reference state can be regarded as a well-defined one-dimensional function of depth, which forms a surface in temperature, salinity, and density space between the surface and the bottom of the ocean. For a very small proportion of water masses, this surface can be multivalued and water parcels can have up to two statically stable levels in the reference density profile, of which the shallowest is energetically more accessible. Classifying parcels from the surface to the bottom gives a different reference density profile than classifying in the opposite direction. However, this difference is negligible. This study shows that the reference state obtained by standard sorting methods is equivalent to, though computationally more expensive than, the volume frequency distribution approach. The approach that is presented can be applied systematically and in a computationally efficient manner to investigate the APE budget of the ocean circulation using models or climatological data

Structural Performance Monitoring Using a Dynamic Data-Driven BIM Environment

Structural health monitoring data has not been fully leveraged to support asset management due to a lack of effective integration with other datasets. A Building Information Modelling (BIM) approach is presented to leverage structural monitoring data in a dynamic manner. The approach allows for the automatic generation of parametric BIM models of structural monitoring systems that include time-series sensor data; and it enables data-driven and dynamic visualisation in an interactive 3D environment. The approach supports dynamic visualisation of key structural performance parameters, allows for the seamless updating and long-term management of data, and facilitates data exchange by generating Industry Foundation Classes (IFC) compliant models. A newly-constructed bridge near Stafford, UK, with an integrated fibre-optic sensor based monitoring system was used to test the capabilities of the developed approach. The case study demonstrated how the developed approach facilitates more intuitive data interpretation, provides a user-friendly interface to communicate with various stakeholders, allows for the identification of malfunctioning sensors thus contributing to the assessment of monitoring system durability, and forms the basis for a powerful data-driven asset management tool. In addition, this project highlights the potential benefits of investing in the development of data-driven and dynamic BIM environments

Resilience theory incorporated into urban wastewater systems management. State of the art

This is the final version of the article. Available from Elsevier via the DOI in this record.Government bodies, utilities, practitioners, and researchers have growing interest in the incorporation of resilience into wastewater management. Since resilience is a multidisciplinary term, it is important to review what has been achieved in the wastewater sector, and describe the future research directions for the forthcoming years. This work presents a critical review of studies that deal with resilience in the wastewater treatment sector, with a special focus on understanding how they addressed the key elements for assessing resilience, such as stressors, system properties, metrics and interventions to increase resilience. The results showed that only 17 peer-reviewed papers and 6 relevant reports, a small subset of the work in wastewater research, directly addressed resilience. The lack of consensus in the definition of resilience, and the elements of a resilience assessment, is hindering the implementation of resilience in wastewater management. To date, no framework for resilience assessment is complete, comprehensive or directly applicable to practitioners; current examples are lacking key elements (e.g. a comprehensive study of stressors, properties and metrics, examples of cases study, ability to benchmark interventions or connectivity with broader frameworks). Furthermore, resilience is seen as an additional cost or extra effort, instead of a means to overcome project uncertainty that could unlock new opportunities for investment.The authors thank the consultancy team in Water Research, Strategic Advisory Services Research in Atkins UK, and Corinne Trommsdorff from IWA, for their constructive comments and support. Their contribution is highly appreciated. This work has been supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642904 - TreatRec ITN-EID project, and by the Ministry of Economy and competitiveness for the Ramon and Cajal grant from Lluís Corominas (RYC-2013-14595) and for the REaCH project (CTM2015-66892-R, MINECO/FEDER, EU). LEQUIA and ICRA were recognized as consolidated research groups by the Catalan Government with codes 2014-SGR-1168 and 2014-SGR-291, respectively. The second and fifth authors acknowledge support from the UK Engineering & Physical Sciences Research Council grant EP/K006924/1

8.2 ka event North Sea hydrography determined by bivalve shell stable isotope geochemistry

The abrupt 8.2 ka cold event has been widely described from Greenland and North Atlantic records. However, its expression in shelf seas is poorly documented, and the temporal resolution of most marine records is inadequate to precisely determine the chronology of major events. A robust hydrographical reconstruction can provide an insight on climatic reaction times to perturbations to the Atlantic Meridional Overturning Circulation. Here we present an annually-resolved temperature and water column stratification reconstruction based on stable isotope geochemistry of Arctica islandica shells from the Fladen Ground (northern North Sea) temporally coherent with Greenland ice core records. Our age model is based on a growth increment chronology obtained from four radiometrically-dated shells covering the 8290–8100 cal BP interval. Our results indicate that a sudden sea level rise (SSLR) event-driven column stratification occurred between ages 8320–8220 cal BP. Thirty years later, cold conditions inhibited water column stratification but an eventual incursion of sub-Arctic waters into the North Sea re-established density-driven stratification. The water temperatures reached their minimum of ~3.7 °C 55 years after the SSLR. Intermittently-mixed conditions were later established when the sub-Arctic waters receded

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses