Management of brainstem haemorrhages

Among spontaneous intracranial haemorrhages, primary non-traumatic brainstem haemorrhages are associated with the highest mortality rate. Patients classically present with rapid neurological deterioration. Previous studies have found that the severity of initial neurological symptoms and hydrocephalus are predictors of poor outcomes. In addition, radiological parameters aim to classify brainstem haematomas according to volume, extension and impact on prognosis. However, previous studies have failed to agree on a differentiated radiological classification for outcome and functional recovery. Electrophysiology, including motor, auditory and somatosensory evoked potentials, is used to estimate the extent of the initial injury and predict functional recovery. The current management of brainstem haematomas remains conservative, focusing on initial close neurocritical care monitoring. Surgical treatment concepts exist, but similarly to general intracranial haemorrhage management, they continue to be controversial and have not been sufficiently investigated. This is especially the case for haematomas in the posterior fossa, as these are excluded from most current clinical trials. Existing studies were mostly carried out before the present millennium began, and limitations are evident in the adaptation of those results and recommendations to current management, with today’s technological and diagnostic possibilities. We therefore recommend the re-evaluation of brainstem haemorrhages in the modern neurosurgical and intensive care environment

Ecological impact assessments fail to reduce risk of bat casualties at wind farms

Demand for renewable energy is rising exponentially. While this has benefits in reducing greenhouse gas emissions, there may be costs to biodiversity [1]. Environmental Impact Assessments (EIAs) are the main tool used across the world to predict the overall positive and negative effects of renewable energy developments before planning consent is given, and the Ecological Impact Assessments (EcIAs) within them assess their species-specific effects. Given that EIAs are undertaken globally, are extremely expensive, and are enshrined in legislation, their place in evidence-based decision making deserves evaluation. Here we assess how well EIAs of wind-farm developments protect bats. We found they do not predict the risks to bats accurately, and even in those cases where high risk was correctly identified, the mitigation deployed did not avert the risk. Given that the primary purpose of an EIA is to make planning decisions evidence-based, our results indicate that EIA mitigation strategies used to date have been ineffective in protecting bats. In the future, greater emphasis should be placed on assessing the actual impacts post-construction and on developing effective mitigation strategies

Self-Transcendent Emotions and Social Media: Exploring the Content and Consumers of Inspirational Facebook Posts

Although a great deal of research has examined the potential negative effects of Facebook, studies also show that Facebook use can lead to various positive effects. This study builds on this positive effects scholarship: together, the two studies presented herein aim to provide an understanding of the inspirational content available on Facebook and the way social media users in the United States encounter, recall, and interact with this content. Results from the quantitative content analysis in Study 1 show that inspirational Facebook posts contain similar frequencies of hope and appreciation of beauty and excellent elicitors when compared with other forms of media and social media. Results from the national survey conducted in Study 2 show that social media users are most often inspired by portrayals of kindness and overcoming obstacles and that Facebook users did not report different sharing behavior as compared with users of other social media sites

Inverse Solidification Induced by Active Janus Particles

Crystals melt when thermal excitations or the concentration of defects in the lattice is sufficiently high. Upon melting, the crystalline long‐range order vanishes, turning the solid to a fluid. In contrast to this classical scenario of solid melting, here a counter‐intuitive behavior of the occurrence of crystalline long‐range order in an initially disordered matrix is demonstrated. This unusual solidification is demonstrated in a system of passive colloidal particles accommodating chemically active defects—photocatalytic Janus particles. The observed crystallization occurs when the amount of active‐defect‐induced fluctuations (which is the measure of the effective temperature) reaches critical value. The driving mechanism behind this unusual behavior is purely internal and resembles a blast‐induced solidification. Here, the role of “internal micro‐blasts” is played by the photochemical activity of defects residing in the colloidal matrix. The defect‐induced solidification occurs under non‐equilibrium conditions: the resulting solid exists as long as a constant supply of energy in the form of ion flow is provided by the catalytic photochemical reaction at the surface of active Janus particle defects. The findings could be useful for the understanding of the phase transitions of matter under extreme conditions far from thermodynamic equilibrium.Inverse solidification driven by active colloids provides novel insight into the collective effects in mixed colloidal systems. It offers versatile possibilities to address the processes of solidification in various systems out of equilibrium, including the formation of bio‐molecular condensates or biomineralization, transitions from amorphous to polycrystalline state in condensed matter, or synthesis of materials under extreme conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162773/3/adfm202003851.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162773/2/adfm202003851-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162773/1/adfm202003851_am.pd

Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model

Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, we investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, which carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-term electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, providing a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple cortical neuron populations, including those stained for interneuron markers. Further histological analysis revealed early localized microglial activation months before neuron loss started in the thalamocortical system and spinal cord, which was accompanied by astrogliosis. This pathology was more pronounced and occurred in the cortex before the thalamus or spinal cord and differed markedly from the staging seen in mouse models of other forms of neuronal ceroid lipofuscinosis. Neonatal administration of adeno-associated virus serotype 9-mediated gene therapy ameliorated the seizure and gait phenotypes and prolonged the life span of Cln2R207X mice, attenuating most pathological changes. Our findings highlight the importance of clinically relevant outcome measures for judging preclinical efficacy of therapeutic interventions for CLN2 disease

IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress

IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface

Micro- and nano-fluidics around HAB cells

Have you ever wondered how algae stay so clean? Most flowering-plant leaves also stay clean. Under air, films of water and “dirt” are repelled. Repulsion forces the water into droplets that easily roll off because these leaves are covered in hydrophobic nm- to µm- sized grooves and pillars, producing superhydrophobicity (SH) at the surface. Similarly, most algal cells bear a glycocalyx of organic fibrils that give surface structure, and are often hydrophobic. Glycocalyxes serve many functions, but whether they produce SH is poorly known. SH coatings are being developed to prevent fouling of ships and aquaculture structures without using toxins, so this technology could help understand how algae defeat fouling. Glycocalyxes are composed of exopolymeric secretions (EPS), and algae sometimes make the water more viscous using this tightly and more loosely bound EPS. EPS is also sometimes sticky. SH cuticles on copepods may change ambient fluid microdynamics by allowing slip at their surfaces, and facilitate filter feeding. By managing ambient viscosity and surface properties including slipping and sticking, algae may have the tools to engineer ambient fluidics and stay clean and unfouled

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

Projections from the Dorsomedial Division of the Bed Nucleus of the Stria Terminalis to Hypothalamic Nuclei in the Mouse

Acknowledgments: All the authors contributed to perform the experiments. SC designed the experiments, analyzed the data and wrote the paper. MB, JAG, DB and PYR edited the manuscript. This work was supported by the Region Franche-Comté, France (PYR), by The Francis Crick Institute (DB), by the Swiss National Science Foundation (PZ00P3_167934/1) and the Novartis Foundation for medical-biological research (19B145) (SC) The data that support the findings of this study are available from the corresponding author upon reasonable request.Peer reviewedPublisher PD

Dual-barrel conductance micropipet as a new approach to the study of ionic crystal dissolution kinetics

A new approach to the study of ionic crystal dissolution kinetics is described, based on the use of a dual-barrel theta conductance micropipet. The solution in the pipet is undersaturated with respect to the crystal of interest, and when the meniscus at the end of the micropipet makes contact with a selected region of the crystal surface, dissolution occurs causing the solution composition to change. This is observed, with better than 1 ms time resolution, as a change in the ion conductance current, measured across a potential bias between an electrode in each barrel of the pipet. Key attributes of this new technique are: (i) dissolution can be targeted at a single crystal surface; (ii) multiple measurements can be made quickly and easily by moving the pipet to a new location on the surface; (iii) materials with a wide range of kinetics and solubilities are open to study because the duration of dissolution is controlled by the meniscus contact time; (iv) fast kinetics are readily amenable to study because of the intrinsically high mass transport rates within tapered micropipets; (v) the experimental geometry is well-defined, permitting finite element method modeling to allow quantitative analysis of experimental data. Herein, we study the dissolution of NaCl as an example system, with dissolution induced for just a few milliseconds, and estimate a first-order heterogeneous rate constant of 7.5 (±2.5) × 10–5 cm s–1 (equivalent surface dissolution flux ca. 0.5 μmol cm–2 s–1 into a completely undersaturated solution). Ionic crystals form a huge class of materials whose dissolution properties are of considerable interest, and we thus anticipate that this new localized microscale surface approach will have considerable applicability in the future