Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of $\textit{RIM15}$, $\textit{YAK1}$ and $\textit{MCK1}$ correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially $\textit{GSY2}$ and $\textit{TPS1}$, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of $\textit{GSY2}$ and $\textit{TSL1}$ or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants ($\textit{rim15Δyak1Δ}$ or $\textit{rim15Δmck1Δ}$). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the $\textit{TOR1}$-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast.This work was sponsored by a scholarship awarded by National University of Defense Technology of China (to LC) and a scholarship from Lucy Cavendish College, Cambridge (to ZQ). Reagents and tools were supported by the UNICELLSYS Collaborative Project (No. 201142) of the European Commission (awarded to SGO). NZ is grateful to the Wellcome Trust and the University of Cambridge for support and facilities

Overrepresentation of Injection Drug Use Route of Infection Among Human Immunodeficiency Virus Long-term Nonprogressors: A Nationwide, Retrospective Cohort Study in China, 1989-2016.

BackgroundWhy some persons living with human immunodeficiency virus (HIV) (PLWH) progress quickly and others remain "healthy" for a decade or more without treatment remains a fundamental question of HIV pathology. We aimed to assess the epidemiological characteristics of HIV long-term nonprogressors (LTNPs) based on a cohort of PLWH in China observed between 1989 and 2016.MethodsWe conducted a nationwide, retrospective cohort study among Chinese PLWH with HIV diagnosed before 1 January 2008. Records were extracted from China's national HIV/AIDS database on 30 June 2016. LTNPs were defined as those with AIDS-free, antiretroviral therapy-naive survival, with CD4 cell counts consistently ≥500/μL for ≥8 years after diagnosis. Prevalence was calculated, characteristics were described, and determinants were assessed by means of logistic regression. Potential sources of bias were also investigated.ResultsOur cohort included 89 201 participants, of whom 1749 (2.0%) were categorized as LTNPs. The injection drug use (IDU) route of infection was reported by 70.7% of LTNPs, compared with only 37.1% of non-LTNPs. The odds of LTNP status were greater among those infected via IDU (adjusted odds ratio [95% confidence interval], 2.28 [1.94-2.68]) and with HIV diagnosed in settings with large populations of persons who inject drugs (1.75 [1.51-2.02] for detention centers, 1.61 [1.39-1.87] for Yunnan, 1.94 [1.62-2.31] for Guangdong, and 2.90 [2.09-4.02] for Xinjiang).ConclusionsOverrepresentation of the IDU route of infection among LTNPs is a surprising finding worthy of further study, and this newly defined cohort may be particularly well suited to exploration of the molecular biological mechanisms underlying HIV long-term nonprogression

Spectroscopy of 3D-trapped particles inside a hollow-core microstructured optical fiber

We report on the demonstration of three-dimensional optical trapping inside the core of a hollow-core microstructured optical fiber specifically designed and fabricated for this purpose. Optical trapping was achieved by means of an external tweezers beam incident transversely on the fiber and focused through the fiber cladding. Trapping was achieved for a range of particle sizes from 1 to 5 μm, and manipulation of the particles in three-dimensions through the entire cross-section of the fiber core was demonstrated. Spectroscopy was also performed on single fluorescent particles, with the fluorescence captured and guided in the fiber core. Video tracking methods allowed the optical traps to be characterized and photobleaching of single particles was also observed and characterized. © 2012 Optical Society of America

Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

Seperation, identification and analysis of pigment (melanin) production in Streptomyces

Nine strains among 180 Streptomyces isolates produce a diffusible dark brown pigment on both peptone-yeast extract agar and synthetic tyrosine-agar. They also show the positive reaction to Ltyrosine or L-dopa substrates. The pigment has been referred to be as merely as dark brown watersolublepigment, as melanoid or melanin. The different carbon and nitrogen sources which influence the pigment production in the Streptomyces isolates were also investigated, and the carotenoid content in the pigment was analyzed. The melanin formation in the Streptomyces species is the key feature for the classification of the Stretomyces grou

Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

Learning Visual Context by Comparison

Finding diseases from an X-ray image is an important yet highly challenging task. Current methods for solving this task exploit various characteristics of the chest X-ray image, but one of the most important characteristics is still missing: the necessity of comparison between related regions in an image. In this paper, we present Attend-and-Compare Module (ACM) for capturing the difference between an object of interest and its corresponding context. We show that explicit difference modeling can be very helpful in tasks that require direct comparison between locations from afar. This module can be plugged into existing deep learning models. For evaluation, we apply our module to three chest X-ray recognition tasks and COCO object detection & segmentation tasks and observe consistent improvements across tasks. The code is available at https://github.com/mk-minchul/attend-and-compare.Comment: ECCV 2020 spotlight pape