Classical Secret Research Articles

Semi-quantum secret sharing protocol with specific bits based on third party

Abstract The fundamental concept of secret sharing involves dividing a secret into multiple parts and distributing them among several participants, who collectively safeguard the secret. When it comes to restoring the secret, cooperation among specific participants is necessary to reconstruct the original secret. Quantum secret sharing (QSS) employs quantum methods to address some limitations of classical secret sharing. Semi-QSS, an advancement of quantum methods, requires fewer quantum resources. Previous semi-quantum protocols demanded at least one participant with full quantum capabilities and randomly generated secret information. This paper introduces a protocol allowing three participants lacking complete quantum capabilities to share secret information of specific bits with the assistance of a third party possessing complete quantum capabilities. Unlike previous approaches, this protocol does not require participants to possess full quantum capabilities and shares secret information of specific bits. These characteristics make the protocol more practical and flexible for real-world applications.

Comparative evaluation of the extracellular production of a polyethylene terephthalate degrading cutinase by Corynebacterium glutamicum and leaky Escherichia coli in batch and fed-batch processes

BackgroundWith a growing global population, the generation of plastic waste and the depletion of fossil resources are major concerns that need to be addressed by developing sustainable and efficient plastic recycling methods. Biocatalytic recycling is emerging as a promising ecological alternative to conventional processes, particularly in the recycling of polyethylene terephthalate (PET). However, cost-effective production of the involved biocatalyst is essential for the transition of enzymatic PET recycling to a widely used industrial technology. Extracellular enzyme production using established organisms such as Escherichia coli or Corynebacterium glutamicum offers a promising way to reduce downstream processing costs.ResultsIn this study, we compared extracellular recombinant protein production by classical secretion in C. glutamicum and by membrane leakage in E. coli. A superior extracellular release of the cutinase ICCGDAQI was observed with E. coli in batch and fed-batch processes on a litre-scale. This phenomenon in E. coli, in the absence of a signal peptide, might be associated with membrane-destabilizing catalytic properties of the expressed cutinase. Optimisations regarding induction, expression temperature and duration as well as carbon source significantly enhanced extracellular cutinase activity. In particular, in fed-batch cultivation of E. coli at 30 °C with lactose as carbon source and inducer, a remarkable extracellular activity (137 U mL−1) and cutinase titre (660 mg L−1) were achieved after 48 h. Literature values obtained with other secretory organisms, such as Bacillus subtilis or Komagataella phaffii were clearly outperformed. The extracellular ICCGDAQI produced showed high efficacy in the hydrolysis of PET textile fibres, either chromatographically purified or unpurified as culture supernatant. In less than 18 h, 10 g L−1 substrate was hydrolysed using supernatant containing 3 mg cutinase ICCGDAQI at 70 °C, pH 9 with terephthalic acid yields of up to 97.8%.ConclusionExtracellular production can reduce the cost of recombinant proteins by simplifying downstream processing. In the case of the PET-hydrolysing cutinase ICCGDAQI, it was even possible to avoid chromatographic purification and still achieve efficient PET hydrolysis. With such production approaches and their further optimisation, enzymatic recycling of PET can contribute to a more efficient and environmentally friendly solution to the industrial recycling of plastics in the future.

A Kind of (n,t)Threshold Quantum State Sharing Scheme Based on Chinese Reminder Theorem

Secret sharing is a key technology of data confidentiality, where one can distribute a secret among agents, and only the authorized agents can recover the original secret. Quantum information technology, including quantum communication, quantum computing can break through the bottlenecks of classical technology in information security and computing speed, based on quantum mechanics, such as quantum superposition, quantum uncertainty, quantum no-cloning and quantum entanglement. By combining quantum technology with classic secret sharing, the concept of quantum state sharing was presented. In this manuscript, a novel kind of (n,t) threshold quantum state sharing scheme is proposed, where the selected t agents among n agents can cooperate to reconstruct the target secret state. For implementing this scheme, the Chinese reminder theorem is introduced during the processing of the secret key distribution. In addition, to show the proposed scheme clearly, a concrete (5,3) example is given. Furthermore, the proof of the correctness of the scheme is shown. Our scheme will improve the development the quantum secret sharing and open up exploring the application of quantum information technology

Cloning and characterization of an aerolysin gene from a marine pathogen Vibrio splendidus

Vibrio splendidus is one of the main pathogens caused diseases with a diversity of marine cultured animals, especially the skin ulcer syndrome in Apostichopus japonicus. However, limited virulence factors have been identified in V. splendidus. In this study, one aerAVs gene coding an aerolysin of V. splendidus was cloned and conditionally expressed in Escherichia coli. The haemolytic activity of the recombinant AerAVs was analyzed. Western blotting was used to study of the secretion pathway of proaerolysin, and it showed that the proaerolysin was secreted via both outer membrane vehicles and classical secretion pathways. Since no active protein of aerolysin was obtained, one aerolysin surface displayed bacterium DH5α/pAT-aerA was constructed, and its haemolytic activity and virulence were determined. The results showed that the AerAVs displayed on the surface showed obvious haemolytic activity and cytotoxic to the coelomocyte of A. japonicus. Artificial immerse infection separately using the DH5α/pAT or DH5α/pAT-aerA was conducted. The result showed that the mortality percent of sea cucumber A. japonicus challenged with DH5α/pAT-aerA was 38.89 % higher than that challenged with the control strain DH5α/pAT, and earlier death occurred. Combined all the results indicates that aerolysin with the haemolytic activity and cytotoxic activity is a virulence factor of V. splendidus.

Quantum Secret Reconstruction

AbstractIn addition to secret splitting, secret reconstruction is another important component of secret sharing. In this paper, the first quantum secret reconstruction protocol is proposed to protect the reconstruction process. Before the protocol, a classical secret is divided into multiple shares that are distributed to the shareholds, respectively. In the presented protocol, the dealer utilizes the secret to encrypt a privacy quantum state, and sends the encrypted state to a combiner who is chosen by the dealer within the shareholders. With the help of other shareholders, the combiner utilizes the properties of cluster states to recover the privacy quantum state. It is shown that the proposed protocol is secure against several common attacks, including external and internal attacks. Compared with classical secret reconstruction protocols, this protocol not only achieves information‐theoretic security of all shares, but is also more efficient due to the reduced distribution and computation cost. To demonstrate the feasibility of the protocol, a corresponding simulation quantum experiment is conducted on the IBM Q. Furthermore, in conjunction with quantum fingerprinting, it can be directly applied to achieve the task of quantum multiple secrets sharing, since the classical shares can be reused in the proposed protocol.

Heterogeneity and Compositional Diversities of Campylobacter jejuni Outer Membrane Vesicles (OMVs) Drive Multiple Cellular Uptake Processes.

Naturally secreted outer membrane vesicles (OMVs) from gut microbes carry diverse cargo, including proteins, nucleic acids, toxins, and many unidentified secretory factors. Bacterial OMVs can shuttle molecules across different cell types as a generalized secretion system, facilitating bacterial pathogenicity and self-survival. Numerous mucosal pathogens, including Campylobacter jejuni (C.jejuni), share a mechanism of harmonized secretion of major virulence factors. Intriguingly, as a common gut pathogen, C.jejuni lacks some classical virulence-associated secretion systems; alternatively, it often employs nanosized lipid-bound OMVs as an intensive strategy to deliver toxins, including secretory proteins, into the target cells. To better understand how the biophysical and compositional attributes of natural OMVs of C.jejuni regulate their cellular interactions to induce a biologically relevant host response, we conducted an in-depth morphological and compositional analysis of naturally secreted OMVs of C.jejuni. Next, we focused on understanding the mechanism of host cell-specific OMVs uptake from the extracellular milieu. We showed that intracellular perfusion of OMVs is mediated by cytosolic as well as multiple endocytic uptake processes due to the heterogenic nature, abundance of surface proteins, and membrane phospholipids acquired from the source bacteria. Furthermore, we used human and avian cells as two different host targets to provide evidence of target cell-specific preferential uptake of OMVs. Together, the present study provides insight into the unique functionality of natural OMVs of C. jejuni at the cellular interface, upholding their potential for multimodal use as prophylactic and therapeutic carriers.

Composition and functions of bacterial membrane vesicles.

Extracellular vesicles are produced by species across all domains of life, suggesting that vesiculation represents a fundamental principle of living matter. In Gram-negative bacteria, membrane vesicles (MVs) can originate either from blebs of the outer membrane or from endolysin-triggered explosive cell lysis, which is often induced by genotoxic stress. Although less is known about the mechanisms of vesiculation in Gram-positive and Gram-neutral bacteria, recent research has shown that both lysis and blebbing mechanisms also exist in these organisms. Evidence has accumulated over the past years that different biogenesis routes lead to distinct types of MV with varied structure and composition. In this Review, we discuss the different types of MV and their potential cargo packaging mechanisms. We summarize current knowledge regarding how MV composition determines their various functions including support of bacterial growth via the disposal of waste material, nutrient scavenging, export of bioactive molecules, DNA transfer, neutralization of phages, antibiotics and bactericidal functions, delivery of virulence factors and toxins to host cells and inflammatory and immunomodulatory effects. We also discuss the advantages of MV-mediated secretion compared with classic bacterial secretion systems and we introduce the concept of quantal secretion.

Structure and formation of the perforated theca defining the Pelagophyceae (Heterokonta), and three new genera that substantiate the diverse nature of the class.

The pelagophytes, a morphologically diverse class of marine heterokont algae, have been historically united only by DNA sequences. Recently we described a novel perforated theca (PT) encasing cells from the Pelagophyceae and hypothesized it may be the first morphological feature to define the class. Here we consolidate that observation, describing a PT for the first time in an additional seven pelagophyte genera, including three genera new to science. We established clonal cultures of pelagophytes collected from intertidal pools located around Australia, and established phylogenetic trees based on nuclear 18S rDNA and plastid rbcL, psaA, psaB, psbA and psbC gene sequences that led to the discovery of three new species: Wyeophycus julieharrissiae and Chromopallida australis form a distinct lineage along with Ankylochrysis lutea within the Pelagomonadales, while Pituiglomerulus capricornicus is sister genus to Chrysocystis fragilis in the Chrysocystaceae (Sarcinochrysidales). Using fixation by high-pressure freezing for electron microscope observations, a distinctive PT was observed in the three new genera described in this paper, as well as four genera not previously investigated: Chrysoreinhardia, Sargassococcus, Sungminbooa and Andersenia. The mechanism of PT formation is novel, being fabricated from rafts in Golgi-derived vesicles before being inserted into an established PT. Extracellular wall and/or mucilage layers assemble exterior to the PT in most pelagophytes, the materials likewise secreted by Golgi-derived vesicles, though the mechanism of secretion is novel. Secretory vesicles never fuse with the plasma membrane as in classic secretion and deposition, but rather relocate extracellularly beneath the PT and disintegrate, the contents having to pass through the PT prior to wall and/or mucilage synthesis. This study substantiates the diverse nature of pelagophytes, and provides further evidence that the PT is a sound morphological feature to define the Pelagophyceae, with all 14 of the 20 known genera studied to date by TEM possessing a PT.

Quantum homomorphic broadcast multi-signature based on homomorphic aggregation

Quantum multi-signature has attracted extensive attention since it was put forward. Beside its own improvement, related research is often combined with other quantum signature. However, this type of quantum signature has one thing in common, that is, the generation and verification of signature depend heavily on the shared classical secret key. In order to increase the reliability of signature, the homomorphic aggregation technique is applied to quantum multi-signature, and then we propose a quantum homomorphic multi-signature protocol. Unlike previous quantum multi-signature protocols, this protocol utilizes homomorphic properties to complete signature generation and verification. In the signature generation phase, entanglement swapping is introduced, so that the individual signatures of multiple users are aggregated into a new multi-signature. The original quantum state is signed by the shared secret key to realize the verification of the signature in the verification phase. The signature process satisfies the homomorphic property, which can improve the reliability of the signature.

SecA2 Associates with Translating Ribosomes and Contributes to the Secretion of Potent IFN-β Inducing RNAs

Protein secretion plays a central role in modulating interactions of the human pathogen Listeria monocytogenes with its environment. Recently, secretion of RNA has emerged as an important strategy used by the pathogen to manipulate the host cell response to its advantage. In general, the Sec-dependent translocation pathway is a major route for protein secretion in L. monocytogenes, but mechanistic insights into the secretion of RNA by these pathways are lacking. Apart from the classical SecA1 secretion pathway, L. monocytogenes also encodes for a SecA paralogue (SecA2) which targets the export of a specific subset of proteins, some of which are involved in virulence. Here, we demonstrated that SecA2 co-sediments with translating ribosomes and provided evidence that it associates with a subset of secreted small non-coding RNAs (sRNAs) that induce high levels of IFN-β response in host cells. We found that enolase, which is translocated by a SecA2-dependent mechanism, binds to several sRNAs, suggesting a pathway by which sRNAs are targeted to the supernatant of L. monocytogenes.

Verifiable quantum secret sharing with multi access structures

In this paper, we propose a verifiable quantum secret sharing scheme. We share multi classical secrets by using the qudit state among the participants based on the different access structures. Moreover, it is possible to check the honesty of participants in the recovery phase. Analyses show that the proposed scheme is secure against internal and external eavesdroppers.

PHISS: Progressive and hierarchical image segmentation-sharing scheme

As a classical secret sharing technique, (k,n) threshold secret image sharing mainly contains the shadow generation phase and the image reconstruction phase. The sensitive secret image is encrypted into n shadows by the dealer in the shadow generation phase, and the secret image can be reconstructed completely by the participants when the number of shadows meet or exceed the threshold k. Previous progressive or hierarchical secret image sharing schemes have some disadvantages (e.g., inflexibility and inefficiency). To solve this problem, we propose a progressive and hierarchical image segmentation-sharing scheme (referred to as PHISS) in this paper. First, the important content region of the sensitive image (called by the target sub-image) is generated by using the proposed image segmentation algorithm. Here the target sub-image refers to the part with the largest amount of information, for instance, the human face in private photo, the pathological region in medical image and the aircraft in military image. Then, in the shadow generation phase, the target sub-image is encrypted into several shadows with hierarchy, and the hierarchies of the generated shadows in the background sub-image are equal. Last, in the reconstruction phase, the background sub-image can be reconstructed completely. The target sub-image has different quality with different number of shadows and different level of shadows. The image can be reconstructed losslessly if and only if all shadows involved. The experimental results and the comparison with similar works demonstrate the feasibility and the superiority of the proposed method.

Advance Sharing of Quantum Shares for Classical Secrets

Secret sharing schemes for classical secrets can be classified into classical secret sharing schemes and quantum secret sharing schemes. Classical secret sharing has been known to be able to distribute some shares before a given secret. On the other hand, quantum mechanics extends the capabilities of secret sharing beyond those of classical secret sharing. We propose quantum secret sharing with the capabilities in designing of access structures more flexibly and realizing higher efficiency beyond those of classical secret sharing, that can distribute some shares before a given secret.

Dissection of grasspea (Lathyrus sativus L.) root exoproteome reveals critical insights and novel proteins

The plant exoproteome is crucial because its constituents greatly influence plant phenotype by regulating physiological characteristics to adapt to environmental stresses. The root exudates constitute a dynamic aspect of plant exoproteome, as its molecular composition ensures a beneficial rhizosphere in a species-specific manner. We investigated the root exoproteome of grasspea, a stress-resilient pulse and identified 2861 non-redundant proteins, belonging to a myriad of functional classes, including root development, rhizosphere augmentation as well as defense functions against soil-borne pathogens. Significantly, we identified 1986 novel exoproteome constituents of grasspea, potentially involved in cell-to-cell communication and root meristem maintenance, among other critical roles. Sequence-based comparison revealed that grasspea shares less than 30 % of its exoproteome with the reports so far from model plants as well as crop species. Further, the exoproteome revealed 65 % proteins to be extracellular in nature and of these, 37 % constituents were predicted to follow unconventional protein secretion (UPS) mode. We validated the UPS for four stress-responsive proteins, which were otherwise predicted to follow classical protein secretion (CPS). Conclusively, we recognized not only the highest number of root exudate proteins, but also pinpointed novel signatures of dicot root exoproteome.

Standard (3,\xa05)-threshold quantum secret sharing by maximally entangled 6-qubit states

In this paper, a standard (3, 5)-threshold quantum secret sharing scheme is presented, in which any three of five participants can resume cooperatively the classical secret from the dealer, but one or two shares contain absolutely no information about the secret. Our scheme can be fulfilled by using the singular properties of maximally entangled 6-qubit states found by Borras. We analyze the scheme’s security by several ways, for example, intercept-and-resend attack, entangle-and-measure attack, and so on. Compared with the other standard threshold quantum secret sharing schemes, our scheme needs neither to use d-level multipartite entangled states, nor to produce shares by classical secret splitting techniques, so it is feasible to be realized.

Sharing Classical Secrets with Continuous-Variable Entanglement: Composable Security and Network Coding Advantage

Secret sharing is a multi-party cryptographic primitive that can be applied to a network of partially distrustful parties for encrypting data that is both sensitive (it must remain secure) and important (it must not be lost or destroyed). When sharing classical secrets (as opposed to quantum states), one can distinguish between protocols that leverage bi-partite quantum key distribution (QKD) and those that exploit multi-partite entanglement. The latter class are known to be vulnerable to so-called participant attacks and, while progress has been made recently, there is currently no analysis that quantifies their performance in the composable, finite-size regime which has become the gold standard for QKD security. Given this - and the fact that distributing multi-partite entanglement is typically challenging - one might well ask: Is there any virtue in pursuing multi-partite entanglement based schemes? Here, we answer this question in the affirmative for a class of secret sharing protocols based on continuous variable graph states. We establish security in a composable framework and identify a network topology, specifically a bottleneck network of lossy channels, and parameter regimes within the reach of present day experiments for which a multi-partite scheme outperforms the corresponding QKD based method in the asymptotic and finite-size setting. Finally, we establish experimental parameters where the multi-partite schemes outperform any possible QKD based protocol. This one of the first concrete compelling examples of multi-partite entangled resources achieving a genuine advantage over point-to-point protocols for quantum communication and represents a rigorous, operational benchmark to assess the usefulness of such resources.

Virus-Induced Tumorigenesis and IFN System.

Simple SummaryThis review aims to collect recent studies on the complex relationship between the host innate response to oncogenic viruses (i.e., HPV, HTLV-1, MCPyV, JCPyV, Herpesviruses, HBV, HCV) and tumorigenic processes by focusing mainly on regulatory crosstalks between viral components and the type I IFN system. It is a picture of new mechanisms by which type I IFNs may be affected and, in turn, affect signaling pathways to mediate anti-proliferative and antiviral responses in virus-induced tumorigenic context. Studies on cellular and viral miRNAs machinery, as well as cellular communication and microenvironment modification via classical secretion mechanisms and extracellular vesicle-mediated delivery are described.Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and inhibiting apoptosis. They counteract the cellular antiviral defense through viral proteins as well as specific cellular effectors involved in virus-induced tumorigenesis. Type I interferons (IFNs) are a family of cytokines critical not only for viral interference but also for their broad range of properties that go beyond the antiviral action. In fact, they can inhibit cell proliferation and modulate differentiation, apoptosis, and migration. However, their principal role is to regulate the development and activity of most effector cells of the innate and adaptive immune responses. Various are the mechanisms by which IFNs exert their effects on immune cells. They can act directly, through IFN receptor triggering, or indirectly by the induction of chemokines, the secretion of further cytokines, or by the stimulation of cells useful for the activation of particular immune cells. All the properties of IFNs are crucial in the host defense against viruses and bacteria, as well as in the immune surveillance against tumors. IFNs may be affected by and, in turn, affect signaling pathways to mediate anti-proliferative and antiviral responses in virus-induced tumorigenic context. New data on cellular and viral microRNAs (miRNAs) machinery, as well as cellular communication and microenvironment modification via classical secretion mechanisms and extracellular vesicles-mediated delivery are reported. Recent research is reviewed on the tumorigenesis induced by specific viruses with RNA or DNA genome, belonging to different families (i.e., HPV, HTLV-1, MCPyV, JCPyV, Herpesviruses, HBV, HCV) and the IFN system involvement.

Role of HSP90 in Cancer.

HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90α and HSP90β are present in the cytoplasm; TRAP1 is present in the mitochondria; and GRP94 is present in the endoplasmic reticulum and is likely secreted due to post-translational modifications (PTM). HSP90 is also secreted into an extracellular environment via an exosome pathway that differs from the classic secretion pathway. Various co-chaperones are necessary for HSP90 to function. Elevated levels of HSP90 have been observed in patients with cancer. Despite this observation, the possible role of HSP90 in cancer was overlooked because the chaperone was also present in extreme amounts in normal cells and was vital to normal cell function, as observed when the drastic adverse effects resulting from gene knockout inhibited the production of this protein. Differences between normal HSP90 and HSP90 of the tumor phenotype have been better understood and have aided in making the chaperone protein a target for cancer drugs. One difference is in the conformation: HSP90 of the tumor phenotype is more susceptible to inhibitors. Since overexpression of HSP90 is a factor in tumorigenesis, HSP90 inhibitors have been studied to combat the adverse effects of HSP90 overexpression. Monotherapies using HSP90 inhibitors have shown some success; however, combination therapies have shown better results and are thus being studied for a more effective cancer treatment.

In Vitro Secretome Analysis Suggests Differential Pathogenic Mechanisms between Fusarium oxysporum f. sp. cubense Race 1 and Race 4.

Banana Fusarium wilt, caused by the fungus pathogen Fusarium oxysporum f. sp. cubense (Foc), is a devastating disease that causes tremendous reductions in banana yield worldwide. Secreted proteins can act as pathogenicity factors and play important roles in the Foc–banana interactions. In this study, a shotgun-based proteomic approach was employed to characterize and compare the secretomes of Foc1 and Foc4 upon banana extract treatment, which detected 1183 Foc1 and 2450 Foc4 proteins. Comprehensive in silico analyses further identified 447 Foc1 and 433 Foc4 proteins in the classical and non-classical secretion pathways, while the remaining proteins might be secreted through currently unknown mechanisms. Further analyses showed that the secretomes of Foc1 and Foc4 are similar in their overall functional characteristics and share largely conserved repertoires of CAZymes and effectors. However, we also identified a number of potentially important pathogenicity factors that are differentially present in Foc1 and Foc4, which may contribute to their different pathogenicity against banana hosts. Furthermore, our quantitative PCR analysis revealed that genes encoding secreted pathogenicity factors differ significantly between Foc1 and Foc4 in their expression regulation in response to banana extract treatment. To our knowledge, this is the first experimental secretome analysis that focused on the pathogenicity mechanism in different Foc races. The results of this study provide useful resources for further exploration of the complicated pathogenicity mechanisms in Foc.

The Road Less Traveled? Unconventional Protein Secretion at Parasite-Host Interfaces.

Protein secretion in eukaryotic cells is a well-studied process, which has been known for decades and is dealt with by any standard cell biology textbook. However, over the past 20 years, several studies led to the realization that protein secretion as a process might not be as uniform among different cargos as once thought. While in classic canonical secretion proteins carry a signal sequence, the secretory or surface proteome of several organisms demonstrated a lack of such signals in several secreted proteins. Other proteins were found to indeed carry a leader sequence, but simply circumvent the Golgi apparatus, which in canonical secretion is generally responsible for the modification and sorting of secretory proteins after their passage through the endoplasmic reticulum (ER). These alternative mechanisms of protein translocation to, or across, the plasma membrane were collectively termed “unconventional protein secretion” (UPS). To date, many research groups have studied UPS in their respective model organism of choice, with surprising reports on the proportion of unconventionally secreted proteins and their crucial roles for the cell and survival of the organism. Involved in processes such as immune responses and cell proliferation, and including far more different cargo proteins in different organisms than anyone had expected, unconventional secretion does not seem so unconventional after all. Alongside mammalian cells, much work on this topic has been done on protist parasites, including genera Leishmania, Trypanosoma, Plasmodium, Trichomonas, Giardia, and Entamoeba. Studies on protein secretion have mainly focused on parasite-derived virulence factors as a main source of pathogenicity for hosts. Given their need to secrete a variety of substrates, which may not be compatible with canonical secretion pathways, the study of mechanisms for alternative secretion pathways is particularly interesting in protist parasites. In this review, we provide an overview on the current status of knowledge on UPS in parasitic protists preceded by a brief overview of UPS in the mammalian cell model with a focus on IL-1β and FGF-2 as paradigmatic UPS substrates.