DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.

Background & aimsThe epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived.MethodsTo address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids.ResultsWe found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon.ConclusionsOur data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro

Bipyrimidine Signatures as a Photoprotective Genome Strategy in G+C-rich Halophilic Archaea

Halophilic Archaea • Experience high levels of ultraviolet (UV) radiation in their environments • Demonstrate high resistance to UV • Are protected by pigmentation and efficient DNA repair • Have high genomic G+C conten

LEARNING HORTICULTURE WITH TAKE HOME MUSHROOM KITS DURING THE COVID-19 LOCKDOWN

PROBLEM Pre-COVID-19 lockdown (2019), we usually organise a mushroom growing practical in the laboratory (lab). After a lab demonstration, students practice culturing mushroom mycelium, spawn and compost preparation. The compost mixed with spawn in plastic bags are incubated in the Mushroom Research Unit for 2 weeks. Once established, students take the compost bags back home to harvest mushrooms. During the COVID-19 lockdown (2020), face to face laboratory mushroom practicals were no longer possible with social distancing requirements (4 sqm per person). We had to live-stream the practical sessions on Zoom to the students from the lab. We were not satisfied with just live-streaming practicals as the students did not get hands-on experience with growing the mushrooms. PLAN During the COVID-19 lockdown, the first author was invited to speak on Nick Kilvert’s ABC Urban Castaway series and was interviewed by ABC Radio National and ABC News online about self-sufficiency and people’s ability to hunt, forage and live off the local land. In the ABC Urban Castaway series (Week 3), there was a feature on growing our own mushrooms to be self-sufficient and how this could be an educational experience during the lockdown. Hence, at the end of May 2020, mushroom kits, with established mycelial colony in compost were provided to the students with instructions for care so that they could have hands-on learning experience of growing and eating their own mushrooms at home. ACTION We provided the students with a mushroom kit each so that they could practice growing mushrooms as well as a food subsistence during the lockdown. They could also practice time-lapse photography on the mushroom growth stages (from pinning, button and mature stages). If they did a good job, they could get 2 or 3 flushes of mushrooms (usually three flushes are harvested commercially). REFLECTION The students learnt how to grow their own mushrooms during the lockdown and post-lockdown as this is a life skill that they can use in the future. Live-streamed practicals provided useful information on how students can collect the spores and produce spawn to grow more of their own mushrooms in the future, becoming potentially self-sufficient in mushrooms! In addition to learning the theory of mushroom production, students gain the life skills to produce their own mushrooms at home

EEG-based grading of Immune Effector Cell-Associated Neurotoxicity Syndrome

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity

Direct evidence of an efficient energy transfer pathway from jellyfish carcasses to a commercially important deep-water species

Here we provide empirical evidence of the presence of an energetic pathway between jellyfish and a commercially important invertebrate species. Evidence of scavenging on jellyfish carcasses by the Norway lobster (Nephrops norvegicus) was captured during two deployments of an underwater camera system to 250–287 m depth in Sognefjorden, western Norway. The camera system was baited with two Periphylla periphylla (Scyphozoa) carcasses to simulate the transport of jellyfish detritus to the seafloor, hereby known as jelly-falls. N. norveigus rapidly located and consumed a large proportion (>50%) of the bait. We estimate that the energy input from jelly-falls may represent a significant contribution to N. norvegicus energy demand (0.21 to 10.7 times the energy required for the population of N. norvegicus in Sognefjorden). This potentially high energetic contribution from jelly-falls highlights a possible role of gelatinous material in the support of commercial fisheries. Such an energetic pathway between jelly-falls and N. norvegicus could become more important with increases in jellyfish blooms in some regions

Neuroprotection Therapy for Traumatic Brain Injury

The main goal of this project was to test the effectiveness of a novel combination neuroprotection therapy for traumatic brain injury (TBI). TBI affects millions of people worldwide every year. Neuroinflammation, excitotoxicity and neuronal death as well as related mechanisms contribute to the development of acute and complex neurological deficits, including post-traumatic seizures and cognitive dysfunction. Neuroprotection approaches targeting acute and chronic phases of TBI are needed to limit the damage and prevent post-TBI dysfunction. A variety of neuroprotection approaches such as statins, progesterone (P), cyclosporine A and anti-inflammatory agents have been tested that either target neurons or non-neuronal cells in animal models of TBI. Herein we evaluated the neuroprotective potential of the neurosteroid Ganaxolone (GX) in a mouse TBI model. GX is a synthetic neurosteroid related to allopregnanolone that has sedative, anxiolytic, and anticonvulsant effects. To our knowledge GX has not been used as a neuroprotective agent for TBI. We utilized a controlled cortical impact (CCI) model, which simulates aspects of concussions, brain contusions, and hemorrhages seen in human TBI. Our pilot studies showed the feasibility of TBI-induced chronic epilepsy model in mice. Ganaxolone treatment had positive outcomes on motor function and additional promising disease-modifying or protective potential to reduce epileptic seizures. This pilot study will be advanced further in a larger cohort to confirm Ganaxolone’s ability to reduce or prevent PTE