Film dynamics and lubricant depletion by droplets moving on lubricated surfaces

Lubricated surfaces have shown promise in numerous applications where impinging foreign droplets must be removed easily; however, before they can be widely adopted, the problem of lubricant depletion, which eventually leads to decreased performance, must be solved. Despite recent progress, a quantitative mechanistic explanation for lubricant depletion is still lacking. Here, we first explained the shape of a droplet on a lubricated surface by balancing the Laplace pressures across interfaces. We then showed that the lubricant film thicknesses beneath, behind, and wrapping around a moving droplet change dynamically with droplet's speed---analogous to the classical Landau-Levich-Derjaguin problem. The interconnected lubricant dynamics results in the growth of the wetting ridge around the droplet, which is the dominant source of lubricant depletion. We then developed an analytic expression for the maximum amount of lubricant that can be depleted by a single droplet. Counter-intuitively, faster moving droplets subjected to higher driving forces deplete less lubricant than their slower moving counterparts. The insights developed in this work will inform future work and the design of longer-lasting lubricated surfaces

Toward shared decision-making in degenerative cervical myelopathy: Protocol for a mixed methods study

Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. DERR1-10.2196/46809. [Abstract copyright: ©Irina Sangeorzan, Grazia Antonacci, Anne Martin, Ben Grodzinski, Carl M Zipser, Rory K J Murphy, Panoraia Andriopoulou, Chad E Cook, David B Anderson, James Guest, Julio C Furlan, Mark R N Kotter, Timothy F Boerger, Iwan Sadler, Elizabeth A Roberts, Helen Wood, Christine Fraser, Michael G Fehlings, Vishal Kumar, Josephine Jung, James Milligan, Aria Nouri, Allan R Martin, Tammy Blizzard, Luiz Roberto Vialle, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Anna MacDowall, Esther Martin-Moore, Martin Burwood, Lianne Wood, Abdul Lalkhen, Manabu Ito, Nicky Wilson, Caroline Treanor, Sheila Dugan, Benjamin M Davies. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.10.2023.

Fishers' behaviour in response to the implementation of a marine protected area

Marine Protected Areas (MPAs) have been widely proposed as a fisheries management tool in addition to their conservation purposes. Despite this, few studies have satisfactorily assessed the dynamics of fishers' adaptations to the loss of fishing grounds. Here we used data from before, during and after the implementation of the management plan of a temperate Atlantic multiple-use MPA to examine the factors affecting the spatial and temporal distribution of different gears used by the artisanal fishing fleet. The position of vessels and gear types were obtained by visual surveys and related to spatial features of the marine park. A hotspot analysis was conducted to identify heavily utilized patches for each fishing gear and time period. The contribution of individual vessels to each significant cluster was assessed to better understand fishers' choices. Different fisheries responded differently to the implementation of protection measures, with preferred habitats of target species driving much of the fishers' choices. Within each fishery, individual fishers showed distinct strategies with some operating in a broader area whereas others kept preferred territories. Our findings are based on reliable methods that can easily be applied in coastal multipurpose MPAs to monitor and assess fisheries and fishers responses to different management rules and protection levels. This paper is the first in-depth empirical study where fishers' choices from artisanal fisheries were analysed before, during and after the implementation of a MPA, thereby allowing a clearer understanding of the dynamics of local fisheries and providing significant lessons for marine conservation and management of coastal systems

MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability

Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function. Accordingly, fibroblasts of affected individuals from one family demonstrated severe depletion of GANP. GANP has been described to function as an mRNA export factor, and to suppress TDP-43-mediated motor neuron degeneration in flies. Thus our results suggest defective mRNA export from nucleus as a potential pathogenic mechanism of axonal degeneration in these patients. The identification of MCM3AP variants in affected individuals from multiple centres establishes it as a disease gene for childhood-onset recessively inherited Charcot-Marie-Tooth neuropathy with intellectual disability.Peer reviewe

The PTEN Phosphatase Controls Intestinal Epithelial Cell Polarity and Barrier Function: Role in Colorectal Cancer Progression

The PTEN phosphatase acts on phosphatidylinositol 3,4,5-triphosphates resulting from phosphatidylinositol 3-kinase (PI3K) activation. PTEN expression has been shown to be decreased in colorectal cancer. Little is known however as to the specific cellular role of PTEN in human intestinal epithelial cells. The aim of this study was to investigate the role of PTEN in human colorectal cancer cells.Caco-2/15, HCT116 and CT26 cells were infected with recombinant lentiviruses expressing a shRNA specifically designed to knock-down PTEN. The impact of PTEN downregulation was analyzed on cell polarization and differentiation, intercellular junction integrity (expression of cell-cell adhesion proteins, barrier function), migration (wound assay), invasion (matrigel-coated transwells) and on tumor and metastasis formation in mice. Electron microscopy analysis showed that lentiviral infection of PTEN shRNA significantly inhibited Caco-2/15 cell polarization, functional differentiation and brush border development. A strong reduction in claudin 1, 3, 4 and 8 was also observed as well as a decrease in transepithelial resistance. Loss of PTEN expression increased the spreading, migration and invasion capacities of colorectal cancer cells in vitro. PTEN downregulation also increased tumor size following subcutaneous injection of colorectal cancer cells in nude mice. Finally, loss of PTEN expression in HCT116 and CT26, but not in Caco-2/15, led to an increase in their metastatic potential following tail-vein injections in mice.Altogether, these results indicate that PTEN controls cellular polarity, establishment of cell-cell junctions, paracellular permeability, migration and tumorigenic/metastatic potential of human colorectal cancer cells

Spearfishing Regulation Benefits Artisanal Fisheries: The ReGS Indicator and Its Application to a Multiple-Use Mediterranean Marine Protected Area

The development of fishing efficiency coupled with an increase of fishing effort led to the overexploitation of numerous natural marine resources. In addition to this commercial pressure, the impact of recreational activities on fish assemblages remains barely known. Here we examined the impact of spearfishing limitation on resources in a marine protected area (MPA) and the benefit it provides for the local artisanal fishery through the use of a novel indicator. We analysed trends in the fish assemblage composition using artisanal fisheries data collected in the Bonifacio Strait Natural Reserve (BSNR), a Mediterranean MPA where the spearfishing activity has been forbidden over 15% of its area. Fish species were pooled into three response groups according to their target level by spearfishing. We developed the new flexible ReGS indicator reflecting shifts in species assemblages according to the relative abundance of each response group facing external pressure. The catch per unit effort (CPUE) increased by ca. 60% in the BSNR between 2000 and 2007, while the MPA was established in 1999. The gain of CPUE strongly depended on the considered response group: for the highly targeted group, the CPUE doubled while the CPUE of the untargeted group increased by only 15.5%. The ReGS value significantly increased from 0.31 to 0.45 (on a scale between 0 and 1) in the general perimeter of this MPA while it has reached a threshold of 0.43, considered as a reference point, in the area protected from spearfishing since 1982. Our results demonstrated that limiting recreational fishing by appropriate zoning in multiple-use MPAs represents a real benefit for artisanal fisheries. More generally we showed how our new indicator may reveal a wide range of impacts on coastal ecosystems such as global change or habitat degradation

Structure of human RNA polymerase III

In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III transcription is observed in cancer and causative Pol III mutations have been described in neurodevelopmental disorders and hypersensitivity to viral infection. Here, we report a cryo-EM reconstruction at 4.0 Å of human Pol III, allowing mapping and rationalization of reported genetic mutations. Mutations causing neurodevelopmental defects cluster in hotspots affecting Pol III stability and/or biogenesis, whereas mutations affecting viral sensing are located in proximity to DNA binding regions, suggesting an impairment of Pol III cytosolic viral DNA-sensing. Integrating x-ray crystallography and SAXS, we also describe the structure of the higher eukaryote specific RPC5 C-terminal extension. Surprisingly, experiments in living cells highlight a role for this module in the assembly and stability of human Pol III