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Atlantic Herring (Clupea harengus) in Northwest Atlantic Fisheries Organization (NAFO) Division 4T, referred to as the southern Gulf of St. Lawrence (sGSL), consists of two spawning components, spring spawners and fall spawners. This document presents the most recent information on trends in abundance, distribution, and harvest for the spring and fall spawning Herring components in NAFO Division 4T. This includes catch-at-age and catch-per-unit-effort (CPUE) indices, fisheries-independent acoustic indices, experimental gillnet survey indices, mesh selectivity, fishery-dependent acoustic indices and catches in the multi-species bottom trawl survey of the sGSL. The data and indices are reported for the sGSL for the spring spawners, and regionally-disaggregated (North, Middle, and South regions) for the fall spawners where applicable. Spring spawners were assessed using a statistical catch at age (SCA) model that allowed for time-varying catchability to the gillnet fishery and time-varying natural mortality. The model estimated that spawning stock biomass (SSB) has been in the critical zone of the Precautionary Approach framework since 2002. The SSB median estimate in April 1 2022 is estimated to be 28,835 tons (t); 62% of the limit reference point (LRP = 46,340 t). Under current low recruitment and high natural mortality conditions, this stock is not expected to recover in the short or the long term. Reducing fishing mortality will have marginal effects on the projected SSB trends. By 2027, the probability of exceeding the LRP was not more than 20% at all catch levels, with SSB values ranging between 32,500 and 35,400 t. Fall spawners were assessed as regionally-disaggregated populations using a SCA model that allowed for time-varying catchability to the gillnet fishery and time-varying natural mortality. Estimated SSB has been declining in all three regions in recent years and is currently in the Cautious Zone of the Precautionary Approach framework. At the target catch level in 2021 (~12,000 t), the probabilities of a 5% increase in SSB by 2024 are all under 40%. Long-term projections show a continuous decline of SSB, however the probability of moving into the Critical Zone (under the LRP) by 2027 was 0% at all catch levels. As a consequence of low productivity and high natural mortality, exploitation of this stock should assert caution until high recruitment is observed for consecutive years. [ABSTRACT FROM AUTHOR]

The southern Gulf of St. Lawrence (sGSL) White Hake Designatable Unit (DU) has been assessed as Endangered by the Committee on the Status of Endangered Wildlife in Canada (COSEWIC). This DU consists primarily of White Hake occurring in the Northwest Atlantic Fishery Organization (NAFO) Division 4T. The Recovery Potential Assessment for this stock found that extremely high natural mortality was preventing the recovery of this stock, while fishing mortality with a bycatch limit of 30 t has a negligible effect on the population trajectory. However, if fishing effort is increased as proposed with the expansion of the Redfish fishery, the impacts of bycatch fisheries on this population may no longer be considered negligible. This report aimed to examine existing information from surveys and fisheries to evaluate whether increased catch levels of Redfish would result in increased bycatch of White Hake. Significant overlap in the spatial distribution of White Hake and Redfish was noted in along the deep waters of the Laurentian Channel. This is partly the result of diet interdependencies among these species and the shift of White Hake to deeper waters to avoid predation. Bycatch of White Hake associated with Redfish was lower at depths greater than 380 m, whereas bycatch was much greater in the months of June, July, and December. Bycatch did not differ significantly based on gear type, however bycatch was overall greater in the southern region of the Laurentian Channel. Overall, the mean value of bycatch was 10.5% in the Redfish fishery. Even in the absence of fishery removals, the sGSL White Hake stock is expected to decline due to extremely high natural mortality. The sGSL White Hake population was projected forward 25 years assuming that productivity would remain at recent levels. SSB was estimated to decline by 38.7% with no catch and 39.3% with annual bycatch of 20 t, the recent level. With annual bycatch of 150 t to 350 t, SSB was estimated to decline by 43% to 48%. With bycatch of 500 t to 1,500 t, SSB declined by 53% to 70%. At present, the White Hake stock is sustained by unusually high recruitment rates which depend largely on a single cohort each year (age 4). The extinction risk for this stock (below 2,000 t) is 22 to 26% with no bycatch up to 150 t, and increases to 30% and 49% at bycatch levels of 350 t to 1,500 t respectively. If recruitment rates were to decline even slightly to the levels seen in the 2000s, the extinction risk for this stock would increase. At the present 30 t bycatch limit for White Hake, White Hake will become a choke species for the future Redfish fishery. [ABSTRACT FROM AUTHOR]

The thyroid gland, a vital component of the endocrine system, plays a pivotal role in regulating metabolic processes, growth, and development. To better characterize thyroid system disrupting chemicals (TSDC), we followed the next-generation risk assessment approach, which further considers the mechanistic profile of xenobiotics. We combined targeted in vitro testing with untargeted metabolomics. Four known TSDC, propyl-thiouracil (PTU), sodium perchlorate, triclosan, and 5-pregnen-3β-ol-20-one-16α‑carbonitrile (PCN) were investigated using rat in vitro models, including primary hepatocytes, PCCL3 cells, thyroid microsomes, and three-dimensional thyroid follicles. We confirmed each compound's mode of action, PTU inhibited thyroperoxidase activity and thyroid hormones secretion in thyroid cells model, sodium perchlorate induced a NIS-mediated iodide uptake decrease as triclosan to a lesser extent, and PCN activated expression and activity of hepatic enzymes (CYPs and UGTs) involved in thyroid hormones metabolism. In parallel, we characterized intracellular metabolites of interest. We identified disrupted basal metabolic pathways, but also metabolites directly linked to the compound's mode of action as tyrosine derivates for sodium perchlorate and triclosan, bile acids involved in beta-oxidation, and precursors of cytochrome P450 synthesis for PCN. This pilot study has provided metabolomic fingerprinting of dedicated TSDC exposures, which could be used to screen and differentiate specific modes of action., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individuals must reproduce to survive and thrive from generation to generation. In fish, the fecundity of individuals and estimates of total reproductive output are critical for evaluating reproductive success and understanding population dynamics. Estimating fecundity is an onerous task; therefore, many populations lack contemporary estimates of fecundity and size-fecundity relationships. However, reproductive dynamics are not static in time; therefore, it is important to develop contemporary fecundity estimates to better inform conservation and management action. To highlight the importance of contemporary fecundity estimates, we examined the fecundity of southern Gulf of St. Lawrence (sGSL) spring and fall spawning Atlantic herring in 2022, developed size-fecundity models, and compared these to historical fecundity estimates and models. Our results suggest that the average fecundity of sGSL spring and fall herring has undergone a substantial temporal decline of approximately 47% and 58%, respectively, since the 1970s and 1980s. The size-fecundity relationships for fall spawning herring have shifted, with fish of a given size exhibiting lower fecundity in 2022 compared to the 1970s. Alternatively, the size-fecundity relationships for spring spawning herring have remained relatively static. Furthermore, simulations highlighted a substantial reduction in potential reproductive output in 2022 compared to 1970 of approximately 32% and 68% for spring and fall spawners, respectively, based on a fixed number of mature females, which may have negative implications for stock rebuilding. Overall, our study provides support for periodic estimates of fecundity in fish populations to better understand temporal changes in reproductive and population dynamics., (© 2024 His Majesty the King in Right of Canada. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.)

Fungi, including filamentous fungi and yeasts, are major contributors to global food losses and waste due to their ability to colonize a very large diversity of food raw materials and processed foods throughout the food chain. In addition, numerous fungal species are mycotoxin producers and can also be responsible for opportunistic infections. In recent years, MALDI-TOF MS has emerged as a valuable, rapid and reliable asset for fungal identification in order to ensure food safety and quality. In this context, this study aimed at expanding the VITEK ® MS database with food-relevant fungal species and evaluate its performance, with a specific emphasis on species differentiation within species complexes. To this end, a total of 380 yeast and mold strains belonging to 51 genera and 133 species were added into the spectral database including species from five species complexes corresponding to Colletotrichum acutatum , Colletotrichum gloeosporioides , Fusarium dimerum , Mucor circinelloides complexes and Aspergillus series nigri. Database performances were evaluated by cross-validation and external validation using 78 fungal isolates with 96.55% and 90.48% correct identification, respectively. This study also showed the capacity of MALDI-TOF MS to differentiate closely related species within species complexes and further demonstrated the potential of this technique for the routine identification of fungi in an industrial context.

Plastids are semi-autonomous organelles like mitochondria and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Excluding the few dozen proteins encoded by the chloroplast and mitochondrial genomes, the majority of plant cell proteins are synthesized by cytosolic ribosomes. Most of these nuclear-encoded proteins are then targeted to specific cell compartments thanks to localization signals present in their amino acid sequence. These signals can be specific amino acid sequences known as transit peptides, or post-translational modifications, ability to interact with specific proteins or other more complex regulatory processes. Furthermore, in eukaryotic cells, protein synthesis can be regulated so that certain proteins are synthesized close to their destination site, thus enabling local protein synthesis in specific compartments of the cell. Previous studies have revealed that such locally translating cytosolic ribosomes are present in the vicinity of mitochondria and emerging views suggest that localized translation near chloroplasts could also occur. However, in higher plants, very little information is available on molecular mechanisms controlling these processes and there is a need to characterize cytosolic ribosomes associated with organelles membranes. To this goal, this protocol describes the purification of higher plant chloroplast and mitochondria and the organelle-associated cytosolic ribosomes., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Nanographene materials are promising building blocks for the growing field of low-dimensional materials for optics, electronics and biophotonics applications. In particular, bottom-up synthesized 0D graphene quantum dots show great potential as single quantum emitters. To fully exploit their exciting properties, the graphene quantum dots must be of high purity; the key parameter for efficient purification being the solubility of the starting materials. Here, we report the synthesis of a family of highly soluble and easily processable rod-shaped graphene quantum dots with fluorescence quantum yields up to 94%. This is uncommon for a red emission. The high solubility is directly related to the design of the structure, allowing for an accurate description of the photophysical properties of the graphene quantum dots both in solution and at the single molecule level. These photophysical properties were fully predicted by quantum-chemical calculations., (© 2023. Springer Nature Limited.)

Recent developments in embedded electronics require the development of micro sources of energy. In this paper, the fabrication of an on-chip interdigitated all-solid-state supercapacitor, using porous gold electrodes and a PVA/KOH quasisolid electrolyte, is demonstrated. The fabrication of the interdigitated porous gold electrode is performed using an original bottom-up approach. A templating method is used for porosity, using a wet chemistry process followed by microfabrication techniques. This paper reports the first example of an all-gold electrode micro-supercapacitor. The supercapacitor exhibits a specific capacitance equal to 0.28 mF·cm -2 and a specific energy of 0.14 mJ·cm -2 . The capacitance value remains stable up to more than 8000 cycles.

The structure and dynamics of networks formed by rod-shaped particles can be indirectly investigated by measuring the diffusion of spherical tracer particles. This method was used to characterize cellulose nanofibril (CNF) networks in both dispersed and arrested states, the results of which were compared with coarse-grained Brownian dynamics simulations. At a CNF concentration of 0.2 wt% a transition was observed where, below this concentration tracer diffusion is governed by the increasing macroscopic viscosity of the dispersion. Above 0.2 wt%, the diffusion of small particles (20-40 nm) remains viscosity controlled, while particles (100-500 nm) become trapped in the CNF network. Sedimentation of silica microparticles (1-5 μm) in CNF dispersions was also determined, showing that sedimentation of larger particles is significantly affected by the presence of CNF. At concentrations of 0.2 wt%, the sedimentation velocity of 5 μm particles was reduced by 99 % compared to pure water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Global warming and drought stress are expected to have a negative impact on agricultural productivity. Desiccation-tolerant species, which are able to tolerate the almost complete desiccation of their vegetative tissues, are appropriate models to study extreme drought tolerance and identify novel approaches to improve the resistance of crops to drought stress. In the present study, to better understand what makes resurrection plants extremely tolerant to drought, we performed transmission electron microscopy and integrative large-scale proteomics, including organellar and phosphorylation proteomics, and combined these investigations with previously published transcriptomic and metabolomics data from the resurrection plant Haberlea rhodopensis . The results revealed new evidence about organelle and cell preservation, posttranscriptional and posttranslational regulation, photosynthesis, primary metabolism, autophagy, and cell death in response to desiccation in H. rhodopensis. Different protective intrinsically disordered proteins, such as late embryogenesis abundant (LEA) proteins, thaumatin-like proteins (TLPs), and heat shock proteins (HSPs), were detected. We also found a constitutively abundant dehydrin in H. rhodopensis whose phosphorylation levels increased under stress in the chloroplast fraction. This integrative multi-omics analysis revealed a systemic response to desiccation in H. rhodopensis and certain targets for further genomic and evolutionary studies on DT mechanisms and genetic engineering towards the improvement of drought tolerance in crops.

The realization of the full objectives of international policies targeting global food security and climate change mitigation, including the United Nation's Sustainable Development Goals, the Paris Climate Agreement COP21 and the European Green Deal, requires that we (i) sustainably increase the yield, nutritional quality and biodiversity of major crop species, (ii) select climate-ready crops that are adapted to future weather dynamic and (iii) increase the resource use efficiency of crops for sustainably preserving natural resources. Ultimately, the grand challenge to be met by agriculture is to sustainably provide access to sufficient, nutritious and diverse food to a worldwide growing population, and to support the circular bio-based economy. Future-proofing our crops is an urgent issue and a challenging goal, involving a diversity of crop species in differing agricultural regimes and under multiple environmental drivers, providing versatile crop-breeding solutions within wider socio-economic-ecological systems. This goal can only be realized by a large-scale, international research cooperation. We call for international action and propose a pan-European research initiative, the CropBooster Program, to mobilize the European plant research community and interconnect it with the interdisciplinary expertise necessary to face the challenge.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Self-assembly is ubiquitous in nature and underlies the formation of many complex systems from the molecular to the macroscopic scale. Kern-Frenkel-like patchy particles are powerful models to investigate this phenomenon by computational methods such as Monte Carlo or molecular dynamics simulations. However, in these models the interactions are mediated by circular patches at the particle surface, which can be hardly mapped to realistic systems, containing for instance faceted particles with rectangular surfaces. In this paper we extend the model to take into account such geometries, and we use it to build a supra coarse-grained model of the cellulose nanocrystal where the interactions are parametrized against all-atomistic molecular dynamics simulations. The formation of cholesteric ribbons and defects in cholesteric droplets of the cellulose nanocrystal are investigated and confirm experimental behavior reported in the literature. The flexibility of this new patchy particle model makes it a powerful tool to develop supra coarse-grained models of self-assembly for large space and time scales and should find a broad range of applications for self-assembly in chemical and biological systems.

U3 snoRNA and the associated Rrp9/U3-55K protein are essential for 18S rRNA production by the SSU-processome complex. U3 and Rrp9 are required for early pre-rRNA cleavages at sites A0, A1 and A2, but the mechanism remains unclear. Substitution of Arg 289 in Rrp9 to Ala (R289A) specifically reduced cleavage at sites A1 and A2. Surprisingly, R289 is located on the surface of the Rrp9 β-propeller structure opposite to U3 snoRNA. To understand this, we first characterized the protein-protein interaction network of Rrp9 within the SSU-processome. This identified a direct interaction between the Rrp9 β-propeller domain and Rrp36, the strength of which was reduced by the R289A substitution, implicating this interaction in the observed processing phenotype. The Rrp9 R289A mutation also showed strong synergistic negative interactions with mutations in U3 that destabilize the U3/pre-rRNA base-pair interactions or reduce the length of their linking segments. We propose that the Rrp9 β-propeller and U3/pre-rRNA binding cooperate in the structure or stability of the SSU-processome. Additionally, our analysis of U3 variants gave insights into the function of individual segments of the 5'-terminal 72-nt sequence of U3. We interpret these data in the light of recently reported SSU-processome structures., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.

Cell compartmentalization is an essential process by which eukaryotic cells separate and control biological processes. Although calmodulins are well-known to regulate catalytic properties of their targets, we show here their involvement in the subcellular location of two plant proteins. Both proteins exhibit a dual location, namely in the cytosol in addition to their association to plastids (where they are known to fulfil their role). One of these proteins, ceQORH, a long-chain fatty acid reductase, was analyzed in more detail, and its calmodulin-binding site was identified by specific mutations. Such a mutated form is predominantly targeted to plastids at the expense of its cytosolic location. The second protein, TIC32, was also shown to be dependent on its calmodulin-binding site for retention in the cytosol. Complementary approaches (bimolecular fluorescence complementation and reverse genetics) demonstrated that the calmodulin isoform CAM5 is specifically involved in the retention of ceQORH in the cytosol. This study identifies a new role for calmodulin and sheds new light on the intriguing CaM-binding properties of hundreds of plastid proteins, despite the fact that no CaM or CaM-like proteins were identified in plastids., (© 2019 Moyet et al.)

The chloroplast is a major plant cell organelle that fulfills essential metabolic and biosynthetic functions. Located at the interface between the chloroplast and other cell compartments, the chloroplast envelope system is a strategic barrier controlling the exchange of ions, metabolites and proteins, thus regulating essential metabolic functions (synthesis of hormones precursors, amino acids, pigments, sugars, vitamins, lipids, nucleotides etc.) of the plant cell. However, unraveling the contents of the chloroplast envelope proteome remains a difficult challenge; many proteins constituting this functional double membrane system remain to be identified. Indeed, the envelope contains only 1% of the chloroplast proteins ( i.e. 0.4% of the whole cell proteome). In other words, most envelope proteins are so rare at the cell, chloroplast, or even envelope level, that they remained undetectable using targeted MS studies. Cross-contamination of chloroplast subcompartments by each other and by other cell compartments during cell fractionation, impedes accurate localization of many envelope proteins. The aim of the present study was to take advantage of technologically improved MS sensitivity to better define the proteome of the chloroplast envelope (differentiate genuine envelope proteins from contaminants). This MS-based analysis relied on an enrichment factor that was calculated for each protein identified in purified envelope fractions as compared with the value obtained for the same protein in crude cell extracts. Using this approach, a total of 1269 proteins were detected in purified envelope fractions, of which, 462 could be assigned an envelope localization by combining MS-based spectral count analyses with manual annotation using data from the literature and prediction tools. Many of such proteins being previously unknown envelope components, these data constitute a new resource of significant value to the broader plant science community aiming to define principles and molecular mechanisms controlling fundamental aspects of plastid biogenesis and functions., (© 2019 Bouchnak et al.)

Chloroplasts are major components of plant cells. Such plastids fulfill many crucial functions, such as assimilation of carbon, sulfur and nitrogen as well as synthesis of essential metabolites. These organelles consist of the following three key sub-compartments. The envelope, characterized by two membranes, surrounds the organelle and controls the communication of the plastid with other cell compartments. The stroma is the soluble phase of the chloroplast and the main site where carbon dioxide is converted into carbohydrates. The thylakoid membrane is the internal membrane network consisting of grana (flat compressed sacs) and lamellae (less dense structures), where oxygenic photosynthesis takes place. The present protocol describes step by step procedures required for the purification, using differential centrifugations and Percoll gradients, of intact chloroplasts from Arabidopsis, and their fractionation, using sucrose gradients, in three sub-compartments (i.e., envelope, stroma, and thylakoids). This protocol also provides instructions on how to assess the purity of these fractions using markers associated to the various chloroplast sub-compartments. The method described here is valuable for subplastidial localization of proteins using immunoblotting, but also for subcellular and subplastidial proteomics and other studies.

Deposition dynamics, crystallization, molecular packing, and electronic mobility of poly(3,4-ethylenedioxythiophene) (PEDOT) thin films are affected by the nature of the substrate. Computational microscopy has been carried out to reveal the morphology-substrate dependence for PEDOT thin films doped with molecular tosylate deposited on different substrates including graphite, Si 3 N 4 , silicon, and amorphous SiO 2 . It is shown that the substrate is instrumental in formation of the lamellar structure. PEDOT films on the ordered substrates (graphite, Si 3 N 4 , and silicon) exhibit preferential face-on orientation, with graphite showing the most ordered and pronounced face-on packing. In contrast, PEDOT on amorphous SiO 2 exhibits the dominant edge-on orientation, except in the dry state where both packings are equally presented. The role of water and the porosity of the substrate in formation of the edge-on structure on SiO 2 is outlined. On the basis of the calculated morphology, the multiscale calculations of the electronic transport and percolative analysis are performed outlining how the character of the substrate affects the electron mobility. It is demonstrated that good crystallinity (PEDOT on graphite substrate) and high content of edge-on (PEDOT on SiO 2 substrate) are not enough to achieve the highest electrical in-plane mobility. Instead, the least ordered material with lower degree of the edge-on content (PEDOT on silicon substrate) provides the highest mobility because it exhibits an efficient network of π-π stacked chain extending throughout the entire sample.

Plastids are semiautonomous organelles like mitochondria, and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions.

Chloroplasts are semiautonomous organelles found in plants and protists. They are surrounded by a double membrane system, or envelope. These envelope membranes contain machineries to import nuclear-encoded proteins, and transporters for ions or metabolites, but are also essential for a range of plastid-specific metabolisms. The inner membrane surrounds a stroma, which is the site of the carbon chemistry of photosynthesis. Chloroplasts also contain an internal membrane system, or thylakoids, where the light phase of photosynthesis occurs. The thylakoid membranes themselves have a bipartite structure, consisting of grana stacks interconnected by stroma lamellae. These thylakoid membranes however form a continuous network that encloses a single lumenal space. Chloroplast-encoded or targeted proteins are thus addressed to various sub-compartments that turn out to be flexible systems and whose main functions can be modulated by alterations in the relative levels of their components. This article describes procedures developed to recover highly purified chloroplast membrane fractions (i.e., envelope, crude thylakoid membranes, as well as the two main thylakoid subdomains, grana and stroma lamellae), starting from Percoll-purified Arabidopsis chloroplasts. Immunological markers are also listed that can be used to assess the purity of these fractions and reveal specific contaminations by other plastid membrane compartments. The methods described here are compatible with chloroplast proteome dynamic studies relying on targeted quantitative proteomic investigations.