Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology

Objective comparison of particle tracking methods

Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers

In-situ yeast fermentation to enhance bioconversion of coconut endosperm waste into larval biomass of hermetia illucens: statistical augmentation of larval lipid content

The aim of this study was to spur the lipid accumulation by larvae of Hermetia illucens or black soldier fly (BSFL) via feeding with yeast fermented medium. The Saccharomyces cerevisiae, a single cell yeast, was introduced at different concentrations (0.02, 0.1, 0.5, 1.0, 2.5 wt %) to execute an in-situ fermentation on coconut endosperm waste. The rearing of BSFL was started simultaneously and the rearing was stopped once the BSFL reached the fifth instar. With the increasing of yeast concentration, the rearing duration of BSFL was shortened from 15.5 to 13.5 days. Moreover, it was found that at 0.5 to 1.0 wt % yeast concentration, the lipid yield and lipid productivity of BSFL were statistically enhanced to their highest peaks, namely, at 49.4% and 0.53 g/day, respectively. With regard to biodiesel composition, BSFL-derived biodiesel contained mainly C12:0, C14:0, C16:0 and C18:1. The higher amount of saturated fatty acids could strengthen the oxidative stability biodiesel produced as compared with non-edible oils or microalgal lipid. At last, the addition of yeast was also found to improve the waste reduction index of coconut endosperm waste (CEW) from 0.31 to 0.40 g/day, heralding the capability of BSFL to valorize organic waste via bioconversion into its biomass to serve as a feedstock for biodiesel production

Microalgae Lipid Characterization

To meet the growing interest of utilizing microalgae biomass in the production of biofuels and nutraceutical and pharmaceutical lipids, we need suitable analytical methods and a comprehensive database for their lipid components. The objective of the present work was to demonstrate methodology and provide data on fatty acid composition, lipid class content and composition, characteristics of the unsaponifiables, and type of chlorophylls of five microalgae. Microalgae lipids were fractionated into TAG, FFA, and polar lipids using TLC, and the composition of fatty acids in total lipids and in each lipid class, hydrocarbons, and sterols were determined by GC-MS. Glyco- and phospholipids were profiled by LC/ESI-MS. Chlorophylls and their related metabolites were qualified by LC/APCI-MS. The melting and crystallization profiles of microalgae total lipids and their esters were analyzed by DSC to evaluate their potential biofuel applications. Significant differences and complexities of lipid composition among the algae tested were observed. The compositional information is valuable for strain selection, downstream biomass fractionation, and utilization

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. METHOD: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. DISCUSSION: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. TRIAL REGISTRATION: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Long-term Incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy

Background Epidemiologic knowledge regarding noncardiovascular and all‐cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence‐based healthcare guidelines. Objectives To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all‐cause mortality in AH and pHCM cats. Animals A total of 1730 client‐owned cats (722 AH, 1008 pHCM) from 21 countries. Methods Retrospective, multicenter, longitudinal, cohort study. Long‐term health data were extracted by medical record review and owner/referring veterinarian interviews. Results Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight‐loss‐vomiting‐diarrhea‐anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All‐cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all‐cause survival was significantly shorter in pHCM (P = .0001). Conclusions and Clinical Importance All‐cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death