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Explaining inter-lab variance in c. elegans N2 lifespan: Making a case for standardized reporting to enhance reproducibility

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EXPERIMENTAL GERONTOLOGY 2021年 156卷 111622页

作者： Urban, Nicholas D. cavataio, Joseph P. Berry, Yasmeen Vang, Brandon Maddali, Anirudh Sukpraphrute, Richard J. Schnell, Santiago Truttmann, Matthias c. Univ Michigan Dept Mol & Integrat Physiol Ann Arbor MI 48109 USA Univ Michigan Undergrad Res Opportun Program Ann Arbor MI 48109 USA Univ Michigan Geriatr Ctr Ann Arbor MI 48109 USA Univ Notre Dame Dept Biol Sci Notre Dame IN 46556 USA Univ Notre Dame Dept Appl & Computat Math & Stat Notre Dame IN 46556 USA

The nematode caenorhabditis elegans is a powerful model organism for studying cell development, apoptosis, neuronal circuits, and aging. The isolate N2 is recognized by the c. elegans community as the reference wild-type strain. Interestingly, the lifespan of presumably isogenic c. elegans N2 worms-even when grown under comparable conditions-varies significantly amongst distinct laboratories. This hinders the inter-laboratory comparability of c. elegans lifespan data and raises questions regarding data interpretation and reproducibility. Here, we hypothesized slight alterations in experimental design and worm handling could explain the observed discrepancies. To test this hypothesis, we collected and assessed data from over 1000 published c. elegans N2 lifespan assays as well as corresponding methodological meta-data. We find that mean N2 lifespans range from approximately 7 days to upwards of 35 days, despite laboratories disclosing seemingly comparable experimental conditions. We further demonstrate that, in addition to temperature, the use of the chemical sterilizer 5-fluoro-2 '-deoxyuridine (FUDR) may change N2 lifespan. Additionally, we observed differences in average N2 lifespan from experiments originating from distinct geographic locations, indicating a potential effect of location-specific factors on experimental outcomes. Taken as a whole, our work indicates the sum of many small, rather than a few critical, differences in experimental conditions may account for the observed variance in N2 lifespan. We also find that the absence of standardized experimental methods and the insufficient disclosure of experiment details in the peer-reviewed literature limits the inter-lab comparability of published results. We thus propose the establishment of a succinct reporting standard for c. elegans lifespan experiments to increase the reliability and reproducibility, and thus scientific value, of these studies.

关键词： N2 c elegans Lifespan Aging Variation Reproducibility

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Nutritive Manganese and Zinc Overdosing in Aging c. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis

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MOLEcULAR NUTRITION & FOOD RESEARcH 2021年第8期65卷 e2001176页

作者： Baesler, Jessica Michaelis, Vivien Stiboller, Michael Haase, Hajo Aschner, Michael Schwerdtle, Tanja Sturzenbaum, Stephen R. Bornhorst, Julia Univ Wuppertal Food Chem Fac Math & Nat Sci Wuppertal Germany Univ Potsdam Dept Food Chem Inst Nutr Sci Nuthetal Germany TraceAge DFG Res Unit 2558 Berlin Germany TU Berlin Dept Food Chem & Toxicol Berlin Germany Albert Einstein Coll Med Dept Mol Pharmacol Neurosci & Pediat Bronx NY 10467 USA IM Sechenov First Moscow State Med Univ Moscow Russia Kings Coll London Fac Life Sci & Med Sch Populat Hlth & Environm Sci Dept Analyt Environm & Forens Sci London England

Scope Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode caenorhabditis elegans (c. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. Methods and Results chronic co-exposure of c. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. conclusions A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

关键词： aging c elegans homeostasis manganese zinc

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Peripheral Guanylate cyclase-c modulation of corticolimbic activation and corticotropin-releasing factor signaling in a rat model of stress-induced colonic hypersensitivity

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NEUROGASTROENTEROLOGY AND MOTILITY 2021年第3期33卷 e14076页

作者： Ligon, casey O. Hannig, Gerhard Greenwood-Van Meerveld, Beverley Univ Oklahoma Hlth Sci Ctr Oklahoma Ctr Neurosci Oklahoma City OK USA Ironwood Pharmaceut Boston MA USA Univ Oklahoma Dept Physiol Hlth Sci Ctr Oklahoma City OK USA

Background Psychological stress is a risk factor for irritable bowel syndrome, a functional gastrointestinal pain disorder featuring abnormal brain-gut connectivity. The guanylate cyclase-c (Gc-c) agonist linaclotide has been shown to relieve abdominal pain in IBS-c and exhibits antinociceptive effects in rodent models of post-inflammatory visceral hypersensitivity. However, the role Gc-c signaling plays in psychological stress-induced visceral hypersensitivity is unknown. Here, we test the hypothesis that Gc-c agonism reverses stress-induced colonic hypersensitivity via inhibition of nociceptive afferent signaling resulting in normalization of stress-altered corticotropin-releasing factor (cRF) expression in brain regions involved in pain perception and modulation. Methods Adult female rats were exposed to water avoidance stress or sham stress for 10 days, and the effects of linaclotide on stress-induced changes in colonic sensitivity, corticolimbic phospho-extracellular signal-regulated kinase (pERK), and cRF expression were measured using a combination of behavioral assessments, immunohistochemistry, and qRT-PcR. Key Results Stressed rats exhibited colonic hypersensitivity and elevated corticolimbic pERK on day 11, which was inhibited by linaclotide. qRT-PcR analysis revealed dysregulated cRF expression in the medial prefrontal cortex, paraventricular nucleus of the hypothalamus, and central nucleus of the amygdala on day 28. Dysregulated cRF expression was not affected by linaclotide treatment. conclusions and Inferences Our results demonstrate that exposure to repeated stress induces chronic colonic hypersensitivity in conjunction with altered corticolimbic activation and cRF expression. Gc-c agonism attenuated stress-induced colonic hypersensitivity and ERK phosphorylation, but had no effect on cRF expression, suggesting the analgesic effects of linaclotide occur independent of stress-driven cRF gene expression in corticolimbic circuitry.

关键词： guanylate cyclase‐ c Irritable bowel syndrome linaclotide nociception stress

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Mechanism of the lifespan extension induced by submaximal SERcA inhibition in c. elegans

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MEcHANISMS OF AGEING AND DEVELOPMENT 2021年 196卷 111474页

作者： Garcia-casas, Paloma Alvarez-Illera, Pilar Fonteriz, Rosalba, I Montero, Mayte Alvarez, Javier Univ Valladolid Fac Med Inst Biol & Mol Genet IBGM Dept Biochem & Mol Biol & Physiol Ramon Y Cajal 7 E-47005 Valladolid Spain CSIC Ramon Y Cajal 7 E-47005 Valladolid Spain

We have reported recently that submaximal inhibition of the Sarco Endoplasmic Reticulum ca2+ ATPase (SERcA) produces an increase in the lifespan of c. elegans worms. We have explored here the mechanism of this increased survival by studying the effect of SERcA inhibition in several mutants of signaling pathways related to longevity. Our data show that the mechanism of the effect is unrelated with the insulin signaling pathway or the sirtuin activity, because SERcA inhibitors increased lifespan similarly in mutants of these pathways. However, the effect required functional mitochondria and both the AMP kinase and TOR pathways, as the SERcA inhibitors were ineffective in the corresponding mutants. The same effects were obtained after reducing SERcA expression with submaximal RNAi treatment. The SERcA inhibitors did not induce ER-stress at the concentrations used, and their effect was not modified by inactivation of the OP50 bacterial food. Altogether, our data suggest that the effect may be due to a reduced ER-mitochondria ca2+ transfer acting via AMPK activation and mTOR inhibition to promote survival.

关键词： c elegans SERcA Thapsigargin Lifespan Endoplasmic reticulum Mitochondria AMP kinase TOR

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APc/c cDH1 ubiquitinates IDH2 contributing to ROS increase in mitosis

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cELLULAR SIGNALLING 2021年 86卷 110087页

作者： Lambhate, Surbhi Bhattacharjee, Debanjan Jain, Nishant CSIR Indian Inst Chem Technol Dept Appl Biol Uppal Rd Hyderabad 500007 India Acad Sci & Innovat Res AcSIR Ghaziabad 201002 India

NADPH is a cofactor used by reactive oxygen species (ROS) scavenging enzymes to block ROS produced in cells. Recently, it was shown that in cancer cells, ROS progressively increases in tune to cell cycle leading to a peak in mitosis. Loss of IDH2 is known to cause severe oxidative stress in cell and mouse models as ROS increases in mitochondria. Therefore, we hypothesized that IDH2, a major NADPH-producing enzyme in mitochondria is ubiquitinated for ROS to increase in mitosis. To test this hypothesis, in cancer cells we examined IDH2 ubiquitination in mitosis and measured the ROS produced. We found that IDH2 is ubiquitinated in mitosis and on inhibiting anaphase-promoting complex/cyclosome (APc/c) IDH2 was stabilized. Further, we observed that overexpressing APc/c coactivator cDH1 decreased IDH2, whereas depleting cDH1 decreased IDH2 ubiquitination. To understand the link between IDH2 ubiquitination and ROS produced in mitosis, we show that overexpressing mitochondria-targeted-IDH1 decreased ROS by increasing NADPH in IDH2 ubiquitinated cells. We conclude that APc/c cDH1 ubiquitinates IDH2, a major NADPH-producing enzyme in mitochondria contributing to ROS increase in mitosis. Based on our results, we suggest that mitosis can be a therapeutic window in mutant IDH2-linked pathologies.

关键词： IDH2 APc c cDH1 NADPH ROS Mitosis

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cRAcK GROWTH IN cARBON AND c-0.5MO STEELS IN HIGH TEMPERATURE HYDROGEN: LABORATORY DATA AND FITNESS FOR SERVIcE MODELLING

CRACK GROWTH IN CARBON AND C-0.5MO STEELS IN HIGH TEMPERATUR...

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ASME Pressure Vessels and Piping conference (PVP)

作者： Rollins, Brandon c. Sutton, Nathaniel DNV Dublin OH 43017 USA Equ Engn Grp Shaker Hts OH USA

ISBN: (纸本)9780791886175

High temperature hydrogen attack (HTHA) is a known degradation mechanism in the refining industry for carbon and low alloy steels operating at temperatures above 400 degrees F in hydrogen service. Historically the integrity of operating equipment subject to these conditions has been ensured by using the empirically derived Nelson curves to identify safe operating regions. This approach was largely successful, but failures still occurred and, in some cases, required overly conservative operational limits. Additionally, this approach did not allow for a defect tolerance approach to fitness for service (FFS) assessments. An on-going joint-industry project (JIP) has been addressing these issues by generating laboratory crack growth data and developing models to apply the acquired knowledge in FFS assessments. A testing program was conducted on three (3) c-0.5 Mo steels to generate crack growth data in hydrogen at a range of temperatures (316 to 399 degrees c [600 to 750 degrees F]), 5.52 MPa (800 psig H-2) hydrogen pressure, and stress intensity values between (10.5 to 35.4 MPavm [9 to 32 ksi root in]). These results were used to validate and refine a crack growth model based on the creep crack growth fracture mechanics approach, c*. The results of the test program and modeling efforts are described in detail.

关键词： Fitness-for-service mechanical properties low alloy carbon steel Hydrogen high temperature hydrogen attack creep c

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An Open Source c code Generator and a Tiny Machine Learning Toolchain for the SENSIPLUS Platform 8

An Open Source C Code Generator and a Tiny Machine Learning ...

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8th IEEE International conference on Smart computing (SMARTcOMP)

作者： Bria, A. Ferrigno, L. Marrocco, c. Molinara, M. Vitelli, M. Ria, A. cicalini, M. Manfredini, G. Bruschi, P. Univ Cassino & Southern Lazio Dept Elect & Informat Engn Cassino Italy Italian Natl Council Reasearch CNR Pisa Italy Sensichips Srl Aprilia Italy Univ Pisa Pisa Italy

ISBN: (纸本)9781665481526

The use of Machine Learning in IoT devices has become the only viable path in today's landscape, where millions of connected devices surround us and increasingly affect our lives. These resource-limited devices interact with the surrounding world via actuators and sensors. Many of these devices use Machine Learning techniques to be able to interpret the world and choose the appropriate action to take. Therefore the purpose of this work is to create a system that allows the application of Machine Learning algorithms directly to the ends of the network, where sensors and actuators reside. The system is designed to rely on the SENSIPLUS smart-sensor as a data acquisition device, and consists of an automatic code generation and compilation system, which through the use of a Toolchain, allows to run artificial intelligence algorithms directly on microcontroller devices.

关键词： Machine Learning IoT Pollution Monitoring Smart city Toolchain c code Generator

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Integrated filler metal/base metal manufacturing via cold spray additive manufacturing for brazing c f /Sic and superalloy

Transactions of Materials Research

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Transactions of Materials Research 2025年第1期1卷

作者： Pengcheng Wang Weihan Liu Lei Gu Hao Ran Xiaoguo Song Zhaoyi Pan Haiyan chen Wenya Li State Key Laboratory of Solidification Processing Shaanxi Key Laboratory of Friction Welding Technologies Northwestern Polytechnical University Xi'an 710072 China State Key Laboratory of Advanced Welding and Joining Harbin Institute of Technology Harbin 150001 China Xi'an Space Engine Company Limited Xi'an 710072 China

A new integrated filler metal/base metal manufacturing method by cold spray additive manufacturing is proposed. The integrated cuTi filler metal/GH3536 and cuTi + W composite filler metal/GH3536 are prepared by cold spray additive manufacturing techniques. The large plastic deformation of cu and Ti particles and the tamping effect of W particles promote the interfacial bonding of particles, which improves the weldability of cold sprayed cuTi + W composite filler metals. Based on the cold sprayed cuTi + W composite filler metal, the c f /Sic composites and GH3536 are successfully brazed, and the typical microstructure and brazing mechanism are investigated. As a result, the shear strength of c f /Sic-GH3536 joint brazed by cold sprayed cuTi + W composite filler metal reaches 77 MPa. This study highlightes the great potential of cold spray additive manufacturing for integrated filler metal/base metal manufacturing in brazing.

关键词： Brazing cold spray additive manufacturing composite filler Interface reaction c f /Sic composite

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African c 3 grass n -alkane distributions & plant chemotaxonomy

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Organic Geochemistry 2025年 208卷

作者： Ruth R. Tweedy caroline A.E. Strömberg Tammo Reichgelt Rahab N. Kinyanjui Mbaluka Kimeu Venanzio Munyaka Kevin T. Uno Department of Earth and Planetary Sciences Harvard University Cambridge MA USA Lamont Doherty Earth Observatory of Columbia University Palisades NY USA Department of Biology University of Washington Seattle WA USA Department of Earth Sciences University of Connecticut Storrs CT USA Palynology and Paleobotany Section Earth Sciences Department National Museums of Kenya Nairobi Kenya Department of Archaeology Max Planck Institute of Geoanthropology Jena Germany East African Herbarium National Museums of Kenya Nairobi Kenya Department of Human Evolutionary Biology Harvard University Cambridge MA USA

Reconstructing past vegetation can elucidate the timing, climate forcings, and biotic mechanisms of ecosystem change. Plant macro- and microfossils are traditionally used to study past vegetation but suffer from production and taphonomic biases, such as underrepresentation of important herbaceous vegetation components. Geochemical proxies can fill this gap, but carbon isotopes (δ 13 c) in isolation are unable to distinguish between structurally different c 3 habitats, such as forests and grasslands. Thus, new geochemical methods to identify grassy c 3 ecosystems are necessary. We present n -alkane chain length distributions of 209 plant specimens from two Kenyan c 3 -dominated ecosystems, representing a wide range of plant functional types (PFTs). We find that c 3 PAcMAD grasses produce exceptionally high abundances of long chain c 33 and c 35 n -alkanes (AcL = 32.7, mean c 33 + c 35 relative abundance = 0.69), unlike other c 3 PFTs which produce low abundances of c 33 and c 35 (AcL = 28.9–30.3, mean c 33 + c 35 relative abundance = 0.0–0.21). This finding highlights the importance of measuring and reporting the c 35 n -alkane. Our data further demonstrate that n -alkane distributions can serve as a proxy for some African c 3 PAcMAD grasses, offering a new paleoecological tool for distinguishing c 3 vegetation types.

关键词： Biomarkers c 3 Grass Africa Leaf wax n -alkanes Paleoecology

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Structure and formation probability of contact interface between adjacent M 23 c 6 in aged Fe-15Mn-3Al-0.7c TWIP steel

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Materials & Design 2025年 256卷

作者： Zhenfeng Xu Dong Hu Jingman Lu Huixin Liu Fengliang Tan Zhenzhen Guo Yang Yang Hunan University of Humanities Science and Technology Loudi Hunan 417000 PR China Zhiyuan Emerging Industry Research Institute Loudi Hunan 417000 PR China

M 23 c 6 carbides are characterized by a complex unit cell structure and high stacking fault (SF) energies, theoretically impeding the formation of SFs within the carbides. However, SFs can form upon contact and coarsening. Given their significance in understanding the deformation mechanism of nano-crystalline structures, their formation mechanisms and probabilities should be clarified. The paper deploys optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to explore the contact interface structures of adjacent grain boundary M 23 c 6 in aged Fe-15Mn-3Al-0.7c high-manganese TWIP steel. Results show the internal lattice of grain boundary M 23 c 6 features a prominent 0.8165-nm-wide SF structure parallel to the close-packed plane. This width is 33.5 % greater than that of the close-packed plane and {1 1 1}γ is found within it. It is proved that the SF is generated by the growth and contact beween adjacent M 23 c 6 carbides. Based on these findings, a new model is established to predict the possible contact interface structures and formation probabilities: a SF structure where remaining austenite planes exist in between (probability: 66.7 %), a coherent interface with SFs when the distance between the nuclei of the two carbides conforms to S = nd/sinθ (probability: 33.3 %), or a coherent interface without SFs (probability: 11.1 %).

关键词： TWIP steel M 23 c 6 Orientation relationship Interface structure Stacking fault

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