Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

Introduction: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data.

A quantitative approach to the spread of variance in translational research using Monte Carlo simulation.

The translation of promising preclinical research into successful trials often fails. One contributing factor is the "Princess and the Pea" problem, which refers to how an initially significant effect size dissipates as research transitions to more complex systems. This work aimed to quantify the effects of spreading variability on sample size requirements.

Mitochondrial-derived compartments: A "fusel alcohol generator" in yeast?

Schuler et al. (2021) demonstrate that mitochondrial-derived compartments protect cells from amino acid toxicity by activation of amino acid catabolism through the Ehrlich pathway, thus highlighting the incredible plasticity of mitochondria in rewiring cellular metabolism.

The enigma of an interconnected mitochondrial reticulum: new insights into mitochondrial fusion.

It has been over 20 years since the identification of the first GTPases that regulate mitochondrial fusion in drosophila, yeast, and mammalian cells. While the molecular identification of these players solidified the new field of mitochondrial dynamics, cell imaging had established the dynamic properties of mitochondria over a century before. The genetic dissection of mitochondrial fusion, fission, and positioning within cells cemented our understanding of the essential nature of this plasticity in health and disease.

Test-retest variability of [ C]ABP688 estimates of metabotropic glutamate receptor subtype 5 availability in humans.

[ C]ABP688 is a positron emission tomography (PET) radioligand that binds selectively to metabotropic glutamate type 5 receptors (mGluR5). The use of this tracer has identified receptor binding changes in clinical populations, and has been informative in drug occupancy studies. However, previous studies have found significant increases in [ C]ABP688 binding in the later scan of same-day comparisons, and estimates of test-retest reliability under consistent scanning conditions are not available.

The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity.

Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro.

Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes.

Peroxisomes function together with mitochondria in a number of essential biochemical pathways, from bile acid synthesis to fatty acid oxidation. Peroxisomes grow and divide from pre-existing organelles, but can also emerge de novo in the cell. The physiological regulation of de novo peroxisome biogenesis remains unclear, and it is thought that peroxisomes emerge from the endoplasmic reticulum in both mammalian and yeast cells.

Mitochondrial Dynamics: ER Actin Tightens the Drp1 Noose.

Drp1 is an oligomeric GTPase essential for mitochondrial division. A recent study has proposed a new model whereby machinery localized to the endoplasmic reticulum drives polymerization of actin, which then acts as a platform for Drp1 oligomerization and hydrolysis at mitochondrial constriction sites.

MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death.

There has been evidence that mitochondrial fragmentation is required for apoptosis, but the molecular links between the machinery regulating dynamics and cell death have been controversial. Indeed, activated BAX and BAK can form functional channels in liposomes, bringing into question the contribution of mitochondrial dynamics in apoptosis. We now demonstrate that the activation of apoptosis triggers MAPL/MUL1-dependent SUMOylation of the fission GTPase Drp1, a process requisite for cytochrome c release.

A sensorimotor role for traveling waves in primate visual cortex.

Traveling waves of neural activity are frequently observed to occur in concert with the presentation of a sensory stimulus or the execution of a movement. Although such waves have been studied for decades, little is known about their function. Here we show that traveling waves in the primate extrastriate visual cortex provide a means of integrating sensory and motor signals.

Tuning cell-surface affinity to direct cell specific responses to patterned proteins.

Interactions with local extracellular cues direct cell migration. A versatile method to study cell response to a protein consists of patterning the protein cue on a substrate and quantifying the distribution of cells between patterned and non-patterned areas. Here, we define the concepts of (i) cell-surface affinity to describe cell choices, and of (ii) reference surface (RS) to clarify that the choice is made relative to a reference.

Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma.

Glioblastomas (GBM) are highly motile cancers that invade through normal brain. In the absence of curative chemotherapy this invasion, beyond surgical and radiotherapy margins, to distant brain sites is thought to be an important cause of treatment failure. Paradoxically, studies analyzing failure patterns have consistently shown that the large majority of failures occur at the original tumor site.

Generation of microisland cultures using microcontact printing to pattern protein substrates.

The capacity to isolate small numbers of neurons in vitro is an essential tool to study the cell biology of synapses and the development of neuronal networks by specific cell types. Microisland culture assays allow for single neurons, or simple neural networks, to be isolated on islands of glial cells; however, the techniques commonly used to produce microisland substrates are expensive, challenging to control, and typically result in many discarded substrates. Here, we used microcontact printing to pattern a glass surface with islands of extracellular matrix proteins known to support neural cell growth and differentiation.

Mitochondrial-ER tethering: the inheritance of a functional unit.

A new study uncovers a novel role for the endoplasmic reticulum in tethering mitochondria specifically at the tip of the growing bud in Saccharomyces cerevisiae. Mitochondrial anchoring to the bud tip requires the tethering factor Mmr1, and the link to the ER is coupled to the cell cycle through a phosphorylation-dependent mechanism.

Role of peripheral endothelin receptors in an animal model of complex regional pain syndrome type 1 (CRPS-I).

Chronic post-ischemic pain (CPIP) is an animal model of CRPS-I developed using a 3-h ischemia-reperfusion injury of the rodent hind paw. The contribution of local endothelin to nociception has been evaluated in CPIP mice by measuring sustained nociceptive behaviors (SNBs) following intraplantar injection of endothelin-1 or -2 (ET-1, ET-2). The effects of local BQ-123 (ETA-R antagonist), BQ-788 (ETB-R antagonist), IRL-1620 (ETB-R agonist) and naloxone (opioid antagonist) were assessed on ET-induced SNBs and/or mechanical and cold allodynia in CPIP mice.

Amyotrophic lateral sclerosis and assisted ventilation: how patients decide.

Background: Throughout the course of their illness, people with amyotrophic lateral sclerosis (ALS) must make many treatment decisions; however, none has such a significant impact on quality of life and survival as decisions about assisted ventilation.

Objective: The purpose of this study was to better understand the experience of decision-making about assisted ventilation for ALS patients.

Methods: Using qualitative phenomenology methodology, 10 semi-structured interviews were conducted with persons with ALS and their caregivers to elicit factors that are pertinent to their decision-making process about assisted ventilation.