Modelling pacemaker oscillations in lymphatic muscle cells: lengthened action potentials by two distinct system effects.

Lymphatic system failures contribute to cardiovascular and various other diseases. A critical function of the lymphatic vascular system is the active pumping of fluid from the interstitium back into the blood circulation by periodic contractions of lymphatic muscle cells (LMCs) in the vessel walls. As in cardiac pacemaking, these periodic contractions can be interpreted as occurring due to linked pacemaker oscillations in the LMC membrane potential (M-clock) and calcium concentration (C-clock).

Membrane Vesicles Can Contribute to Cellulose Degradation by Teredinibacter turnerae, a Cultivable Intracellular Endosymbiont of Shipworms.

Teredinibacter turnerae is a cultivable cellulolytic Gammaproteobacterium (Cellvibrionaceae) that commonly occurs as an intracellular endosymbiont in the gills of wood-eating bivalves of the family Teredinidae (shipworms). The genome of T. turnerae encodes a broad range of enzymes that deconstruct cellulose, hemicellulose and pectin and contribute to wood (lignocellulose) digestion in the shipworm gut.

Codesign of a Neurological Physiotherapy Student-Led Clinic With Students and Patients: An Exploratory Qualitative Study.

Introduction: This study explores students' and patients' views of a UK physical therapy student-led clinic (SLC) for neurological rehabilitation and, using a codesign approach, it proposes an optimal design of a physical therapy SLC for neurological rehabilitation for patient participation and student learning.

Review Of Literature: There is a paucity of literature examining experiences of neurological rehabilitation SLCs. Although research supports the utilization of codesign methodologies with patients and for curriculum development, there remains a gap regarding its application to SLCs in physical therapy for individuals with neurological conditions.

Learning From Human Attention for Attribute-Assisted Visual Recognition.

With prior knowledge of seen objects, humans have a remarkable ability to recognize novel objects using shared and distinct local attributes. This is significant for the challenging tasks of zero-shot learning (ZSL) and fine-grained visual classification (FGVC), where the discriminative attributes of objects have played an important role. Inspired by human visual attention, neural networks have widely exploited the attention mechanism to learn the locally discriminative attributes for challenging tasks.

The Ihara zeta function as a partition function for network structure characterisation.

Statistical characterizations of complex network structures can be obtained from both the Ihara Zeta function (in terms of prime cycle frequencies) and the partition function from statistical mechanics. However, these two representations are usually regarded as separate tools for network analysis, without exploiting the potential synergies between them. In this paper, we establish a link between the Ihara Zeta function from algebraic graph theory and the partition function from statistical mechanics, and exploit this relationship to obtain a deeper structural characterisation of network structure.

The F plasmid conjutome: the repertoire of proteins translocated through an F-encoded type IV secretion system.

Unlabelled: Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic resistance genes. Using the Cre Recombinase Assay for Translocation (CRAfT), we recently reported that the IncFV pED208 conjugation system also translocates at least 16 plasmid-encoded proteins to recipient bacteria. Here, we deployed a high-throughput CRAfT screen to identify the repertoire of chromosomally encoded protein substrates of the pED208 system.

Sleeping for One Week on a Temperature-Controlled Mattress Cover Improves Sleep and Cardiovascular Recovery.

Body temperature should be tightly regulated for optimal sleep. However, various extrinsic and intrinsic factors can alter body temperature during sleep. In a free-living study, we examined how sleep and cardiovascular health metrics were affected by sleeping for one week with (Pod ON) vs.

Membrane vesicles can contribute to cellulose degradation by , a cultivable intracellular endosymbiont of shipworms.

is a cultivable cellulolytic Gammaproteobacterium (Cellvibrionaceae) that commonly occurs as an intracellular endosymbiont in the gills of wood-eating bivalves of the family Teredinidae (shipworms). The genome of encodes a broad range of enzymes that deconstruct cellulose, hemicellulose, and pectin and contribute to wood (lignocellulose) digestion in the shipworm gut. However, the mechanisms by which secretes lignocellulolytic enzymes are incompletely understood.

Microtubule destabilization with colchicine increases the work output of myocardial slices.

Cardiac microtubules have recently been implicated in mechanical dysfunction during heart failure. However, systemic intolerance and non-cardiac effects of microtubule-depolymerizing compounds have made it challenging to determine the effect of microtubules on myocardial performance. Herein, we leverage recent advancements in living myocardial slices to develop a stable working preparation that recapitulates the complexity of diastole by including early and late phases of diastolic filling.

A dual-clock-driven model of lymphatic muscle cell pacemaking to emulate knock-out of Ano1 or IP3R.

Lymphatic system defects are involved in a wide range of diseases, including obesity, cardiovascular disease, and neurological disorders, such as Alzheimer's disease. Fluid return through the lymphatic vascular system is primarily provided by contractions of muscle cells in the walls of lymphatic vessels, which are in turn driven by electrochemical oscillations that cause rhythmic action potentials and associated surges in intracellular calcium ion concentration. There is an incomplete understanding of the mechanisms involved in these repeated events, restricting the development of pharmacological treatments for dysfunction.

IP3R1 underlies diastolic ANO1 activation and pressure-dependent chronotropy in lymphatic collecting vessels.

Pressure-dependent chronotropy of murine lymphatic collecting vessels relies on the activation of the Ca2+-activated chloride channel encoded by Anoctamin 1 (Ano1) in lymphatic muscle cells. Genetic ablation or pharmacological inhibition of ANO1 results in a significant reduction in basal contraction frequency and essentially complete loss of pressure-dependent frequency modulation by decreasing the rate of the diastolic depolarization phase of the ionic pacemaker in lymphatic muscle cells (LMCs). Oscillating Ca2+ release from sarcoendoplasmic reticulum Ca2+ channels has been hypothesized to drive ANO1 activity during diastole, but the source of Ca2+ for ANO1 activation in smooth muscle remains unclear.

A Randomized Trial Examining the Impact of Timing of Intradialytic Cycling on Intradialytic Hypotension.

Introduction: Intradialytic cycling is often performed during the first half of hemodialysis because of concerns regarding increased frequency of intradialytic hypotension (IDH) late in hemodialysis. This increases exercise program resource needs and limits utility of intradialytic cycling to treat dialysis-related symptoms.

Methods: This multicenter, randomized, crossover trial compared IDH rate when cycling during the first half versus the second half of hemodialysis in 98 adults on maintenance hemodialysis.

Some magnetic resonance imaging findings may predict future low back pain and disability: a systematic review.

Questions: Do magnetic resonance imaging (MRI) findings predict future low back pain (LBP), associated disability and global recovery in people with current LBP? Do MRI findings predict these outcomes in people with no current LBP? Do MRI findings predict these outcomes in a mixed sample of people with and without current LBP?

Design: This review is an update of a previous systematic review investigating the relationship between lumbar spine MRI findings and future LBP.

Participants: People with or without LBP with lumbar MRI scans.

Outcome Measures: MRI findings, pain and disability.

Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials.

Objective: To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS).

Methods: Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis.

Methods for Estimating Long-Term Outcomes for Trastuzumab Deruxtecan in HER2-Positive Unresectable or Metastatic Breast Cancer After Two or More Anti-HER2 Therapies.

Background: DESTINY-Breast01 (NCT03248492) is a phase II single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with human epidermal growth factor receptor 2-positive (HER2+) unresectable or metastatic breast cancer (u/mBC) who have received two or more prior anti-HER2 therapies.

Objectives: Objectives were to explore approaches for estimating long-term overall survival (OS) with T-DXd from immature data (June 2020 data-cut; median follow-up 20.5 months), and compare predicted long-term outcomes with UK-recommended non-targeted therapies eribulin, capecitabine, and vinorelbine.

[2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes.

Aromatic ring isosteres and rigidified saturated hydrocarbons are important motifs to enable drug discovery. Herein we disclose [2]-ladderanes as a class of meta-substituted aromatic ring isosteres and rigidified cyclohexanes. A straightforward synthesis of the building blocks is presented along with representative derivatization.

Regionwise Generative Adversarial Image Inpainting for Large Missing Areas.

Recently, deep neural networks have achieved promising performance for in-filling large missing regions in image inpainting tasks. They have usually adopted the standard convolutional architecture over the corrupted image, leading to meaningless contents, such as color discrepancy, blur, and other artifacts. Moreover, most inpainting approaches cannot handle well the case of a large contiguous missing area.

Stabilization of antithetic control via molecular buffering.

A key goal in synthetic biology is the construction of molecular circuits that robustly adapt to perturbations. Although many natural systems display perfect adaptation, whereby stationary molecular concentrations are insensitive to perturbations, its engineering has proven elusive. The discovery of the antithetic control motif was a significant step towards a universal mechanism for engineering perfect adaptation.

Two-Level Graph Neural Network.

Graph neural networks (GNNs) are recently proposed neural network structures for the processing of graph-structured data. Due to their employed neighbor aggregation strategy, existing GNNs focus on capturing node-level information and neglect high-level information. Existing GNNs, therefore, suffer from representational limitations caused by the local permutation invariance (LPI) problem.