Learning-associated astrocyte ensembles regulate memory recall.

The physical manifestations of memory formation and recall are fundamental questions that remain unresolved. At the cellular level, ensembles of neurons called engrams are activated by learning events and control memory recall. Astrocytes are found in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity.

Environmental stress reduces shark residency to coral reefs.

Coral reef ecosystems are highly threatened and can be extremely sensitive to the effects of climate change. Multiple shark species rely on coral reefs as important habitat and, as such, play a number of significant ecological roles in these ecosystems. How environmental stress impacts routine, site-attached reef shark behavior, remains relatively unexplored.

Microvascular plasticity in mouse stroke model recovery: Anatomy statistics, dynamics measured by longitudinal two-photon angiography, network vectorization.

This manuscript quantitatively investigates remodeling dynamics of the cortical microvascular network (thousands of connected capillaries) following photothrombotic ischemia (cubic millimeter volume, imaged weekly) using a novel two-photon angiography and high throughput vascular vectorization method. The results suggest distinct temporal patterns of cerebrovascular plasticity, with acute remodeling peaking at one week post-stroke. The network architecture then gradually stabilizes, returning to a new steady state after four weeks.

Histone serotonylation regulates ependymoma tumorigenesis.

Bidirectional communication between tumours and neurons has emerged as a key facet of the tumour microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, in which alterations in gene expression influence cell states and interactions with the tumour microenvironment. Ependymoma (EPN) is a paediatric brain tumour that relies on epigenomic remodelling to engender malignancy; however, how these epigenetic mechanisms intersect with extrinsic neuronal signalling during EPN tumour progression is unknown.

Astrocytes remember inflammation.

Astrocytes respond to all forms of central nervous system maladies. In a recent issue of Nature, Lee et al. demonstrate that astrocytes encode inflammatory stimuli as epigenetic memory, which strengthens responses to subsequent stimuli and exacerbates pathology in disease models.

Comparative Transcriptomic Analysis of Cerebellar Astrocytes across Developmental Stages and Brain Regions.

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point.

Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke.

Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors.

Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and Calprotectin over one year of treatment with Elexacaftor-Tezacaftor-Ivacaftor in people with CF aged ≥12 years - The RECOVER study.

Background: RECOVER is a multicentre post-approval study of Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pwCF in Ireland and the UK. The CFAbd-Score is the first validated CF-specific patient reported outcome measure (PROM) focusing on gastrointestinal symptoms; it comprises 28 items in 5 domains. In a preliminary study, we previously reported reductions in abdominal symptoms (AS) in pwCF after 26 weeks of ETI-therapy using the CFAbd-Score.

Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial.

Clinical trials have shown that use of elexacaftor/tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. RECOVER is a real-world study designed to measure the impact of ETI in people with CF.

Anguillid eels.

Anguillid eels have fascinated humans for centuries, but our knowledge of these mysterious fish is still scant. There are 19 species or subspecies in the genus Anguilla, which are found globally, except in the eastern Pacific and southern Atlantic. Their common label 'freshwater eels' is a misnomer - all anguillids are facultatively catadromous, born in marine environments, developing in continental waters, with a proportion never entering freshwater at all.

The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6-11 with cystic fibrosis in a real-world setting.

Background: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV in children with Cystic Fibrosis (CF) aged 6-11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6-11 years.

Remote neuronal activity drives glioma progression through SEMA4F.

The tumour microenvironment plays an essential role in malignancy, and neurons have emerged as a key component of the tumour microenvironment that promotes tumourigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bidirectional signalling between tumours and neurons that propagates a vicious cycle of proliferation, synaptic integration and brain hyperactivity; however, the identity of neuronal subtypes and tumour subpopulations driving this phenomenon is incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumours promote progression and widespread infiltration.

Remote neuronal activity drives glioma infiltration via Sema4f.

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration.

Validation of a digit symbol substitution test for use in supervised and unsupervised assessment in mild Alzheimer's disease.

Introduction: The Digit-Symbol-Substitution Test (DSST) is used widely in neuropsychological investigations of Alzheimer's Disease (AD). A computerized version of this paradigm, the DSST-Meds, utilizes medicine-date pairings and has been developed for administration in both supervised and unsupervised environments. This study determined the utility and validity of the DSST-Meds for measuring cognitive dysfunction in early AD.

Targeting of Glycosaminoglycans in Genetic and Inflammatory Airway Disease.

In the lung, glycosaminoglycans (GAGs) are dispersed in the extracellular matrix (ECM) occupying the interstitial space between the capillary endothelium and the alveolar epithelium, in the sub-epithelial tissue and in airway secretions. In addition to playing key structural roles, GAGs contribute to a number of physiologic processes ranging from cell differentiation, cell adhesion and wound healing. Cytokine and chemokine-GAG interactions are also involved in presentation of inflammatory molecules to respective receptors leading to immune cell migration and airway infiltration.

Diamond Raman laser and Yb fiber amplifier for multiphoton fluorescence microscopy.

Here we introduce a fiber amplifier and a diamond Raman laser that output high powers (6.5 W, 1.3 W) at valuable wavelengths (1060 nm, 1250 nm) for two-photon excitation of red-shifted fluorophores.

Current evidence on the effect of highly effective CFTR modulation on interleukin-8 in cystic fibrosis.

Introduction: Cystic fibrosis (CF) is a genetically inherited disease, with mortality and morbidity associated with respiratory disease. The inflammatory response in CF is characterized by excessive neutrophil influx to the airways, mainly due to the increased local production and retention of interleukin-8 (IL-8), a potent neutrophil chemoattractant.

Areas Covered: We discuss how the chemokine IL-8 dominates the inflammatory profile of the airways in CF lung disease.

Segmentation-Less, Automated, Vascular Vectorization.

Recent advances in two-photon fluorescence microscopy (2PM) have allowed large scale imaging and analysis of blood vessel networks in living mice. However, extracting network graphs and vector representations for the dense capillary bed remains a bottleneck in many applications. Vascular vectorization is algorithmically difficult because blood vessels have many shapes and sizes, the samples are often unevenly illuminated, and large image volumes are required to achieve good statistical power.

'Carbon-Monoxide-Releasing Molecule-2 (CORM-2)' Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects.

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological 'gasotransmitter', in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, RuCl(CO)), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release.

Reactive astrocytes facilitate vascular repair and remodeling after stroke.

Brain injury causes astrocytes to assume a reactive state that is essential for early tissue protection, but how reactive astrocytes affect later reparative processes is incompletely understood. In this study, we show that reactive astrocytes are crucial for vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data reveals substantial activation of transcriptional programs related to vascular remodeling after stroke.

Analysing detection gaps in acoustic telemetry data to infer differential movement patterns in fish.

A wide array of technologies are available for gaining insight into the movement of wild aquatic animals. Although acoustic telemetry can lack the fine-scale spatial resolution of some satellite tracking technologies, the substantially longer battery life can yield important long-term data on individual behavior and movement for low per-unit cost. Typically, however, receiver arrays are designed to maximize spatial coverage at the cost of positional accuracy leading to potentially longer detection gaps as individuals move out of range between monitored locations.

A comparison of anterior knee pain, kneeling pain and functional outcomes in suprapatellar versus infrapatellar tibial nailing.

Introduction: Anterior knee pain and kneeling pain are some of the most common complications following intramedullary nailing of tibial shaft fractures. With the increased uptake of suprapatellar nailing at our institution, we undertook a service evaluation to assess anterior knee pain and kneeling pain in patients who underwent the suprapatellar tibial nailing technique compared with the infrapatellar approach.

Methodology: Data from all consecutive intramedullary tibial nailing operations between January 2014 and July 2017 were analysed from a prospectively collected database.

Chain-folded lamellar structure and dynamics of the crystalline fraction of Bombyx mori silk fibroin and of (Ala-Gly-Ser-Gly-Ala-Gly) model peptides.

Solid-state NMR is a powerful analytical technique to determine the composite structure of Bombyx mori silk fibroin (SF). In our previous paper, we proposed a lamellar structure for Ala-Gly copolypeptides as a model of the crystalline fraction in Silk II. In this paper, the structure and dynamics of the crystalline fraction and of a better mimic of the crystalline fraction, (Ala-Gly-Ser-Gly-Ala-Gly) (n = 2-5, 8), and C selectively labeled [3-C]Ala-(AGSGAG) in Silk II forms, were studied using structural and dynamical analyses of the Ala Cβ peaks in C cross polarization/ magic angle spinning NMR and C solid-state spin-lattice relaxation time (T) measurements, respectively.

A Window of Vascular Plasticity Coupled to Behavioral Recovery after Stroke.

Stroke causes remodeling of vasculature surrounding the infarct, but whether and how vascular remodeling contributes to recovery are unclear. We established an approach to monitor and compare changes in vascular structure and blood flow with high spatiotemporal precision after photothrombotic infarcts in motor cortex using longitudinal 2-photon and multiexposure speckle imaging in mice of both sexes. A spatially graded pattern of vascular structural remodeling in peri-infarct cortex unfolded over the first 2 weeks after stroke, characterized by vessel loss and formation, and selective stabilization of a subset of new vessels.

A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.

Background: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS.