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J.R.R. Tolkien in The Lord of the Rings accurately portrayed the signs and symptoms of what is currently labeled Post Traumatic Stress Disorder. Frodo’s condition logically follows his experiences of less than a year in the War of the Ring. Tolkien did not have access to a diagnostic manual but apparently used his keen observations from both World Wars to inform his narrative. No fantasy is employed to describe Frodo condition after the Ring is destroyed. His condition is that of a vet with PTSD. Evidence from the History of Middle-earth demonstrates the deliberate steps taken to show Frodo as broken by his sacrifice. [ABSTRACT FROM AUTHOR]

Research on the security of lattice-based public-key encryption schemes against misuse attacks is an important part of the cryptographic assessment of the National Institute of Standards and Technology (NIST) post-quantum cryptography (PQC) standardization process. In particular, many NIST-PQC cryptosystems follow the same meta-cryptosystem. At EUROCRYPT 2019, B a ˘ etu et al. mounted a classical key recovery under plaintext checking attacks (KR-PCA) and a quantum key recovery under chosen ciphertext attacks (KR-CCA). They analyzed the security of the weak version of nine submissions to NIST. In this paper, we focus on learning with error (LWE)-based FrodoPKE, whose IND-CPA security is tightly related to the hardness of plain LWE problems. We first review the meta-cryptosystem and quantum algorithm for solving quantum LWE problems. Then, we consider the case where the noise follows a discrete Gaussian distribution and recompute the success probability for quantum LWE by using Hoeffding bound. Finally, we give a quantum key recovery algorithm based on LWE under CCA attack and analyze the security of Frodo. Compared with the existing work of B a ˘ etu et al., our method reduces the number of queries from 2 2 to 1 with the same success probability. [ABSTRACT FROM AUTHOR]

Research on the security of lattice-based public-key encryption schemes against misuse attacks is an important part of the cryptographic assessment of the National Institute of Standards and Technology (NIST) post-quantum cryptography (PQC) standardization process. In particular, many NIST-PQC cryptosystems follow the same meta-cryptosystem. At EUROCRYPT 2019, Ba˘etu et al. mounted a classical key recovery under plaintext checking attacks (KR-PCA) and a quantum key recovery under chosen ciphertext attacks (KR-CCA). They analyzed the security of the weak version of nine submissions to NIST. In this paper, we focus on learning with error (LWE)-based FrodoPKE, whose IND-CPA security is tightly related to the hardness of plain LWE problems. We first review the meta-cryptosystem and quantum algorithm for solving quantum LWE problems. Then, we consider the case where the noise follows a discrete Gaussian distribution and recompute the success probability for quantum LWE by using Hoeffding bound. Finally, we give a quantum key recovery algorithm based on LWE under CCA attack and analyze the security of Frodo. Compared with the existing work of Ba˘etu et al., our method reduces the number of queries from 22 to 1 with the same success probability.

Lattice-based cryptography is one of the most promising candidates being considered to replace current public-key systems in the era of quantum computing. In 2016, Bos et al. proposed the key exchange scheme FrodoCCS, that is also a submission to the NIST post-quantum standardization process, modified as a key encapsulation mechanism (FrodoKEM). The security of the scheme is based on standard lattices and the learning with errors problem. Due to the large parameters, standard latticebased schemes have long been considered impractical on embedded devices. The FrodoKEM proposal actually comes with parameters that bring standard lattice-based cryptography within reach of being feasible on constrained devices. In this work, we take the final step of efficiently implementing the scheme on a low-cost FPGA and microcontroller devices and thus making conservative post-quantum cryptography practical on small devices. Our FPGA implementation of the decapsulation (the computationally most expensive operation) needs 7,220 look-up tables (LUTs), 3,549 flip-flops (FFs), a single DSP, and only 16 block RAM modules. The maximum clock frequency is 162 MHz and it takes 20.7 ms for the execution of the decapsulation. Our microcontroller implementation has a 66% reduced peak stack usage in comparison to the reference implementation and needs 266 ms for key pair generation, 284 ms for encapsulation, and 286 ms for decapsulation. Our results contribute to the practical evaluation of a post-quantum standardization candidate.

Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional coactivator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination. [ABSTRACT FROM AUTHOR]

Background: Dacts are multi-domain adaptor proteins. They have been implicated in Wnt and Tgfβ signaling and serve as a nodal point in regulating many cellular activities. Dact genes have so far only been identified in bony vertebrates. Also, the number of Dact genes in a given species, the number and roles of protein motifs and functional domains, and the overlap of gene expression domains are all not clear. To address these problems, we have taken an evolutionary approach, screening for Dact genes in the animal kingdom and establishing their phylogeny and the synteny of Dact loci. Furthermore, we performed a deep analysis of the various Dact protein motifs and compared the expression patterns of different Dacts. Results: Our study identified previously not recognized dact genes and showed that they evolved late in the deuterostome lineage. In gnathostomes, four Dact genes were generated by the two rounds of whole genome duplication in the vertebrate ancestor, with Dact1/3 and Dact2/4, respectively, arising from the two genes generated during the first genome duplication. In actinopterygians, a further dact4r gene arose from retrotranscription. The third genome duplication in the teleost ancestor, and subsequent gene loss in most gnathostome lineages left extant species with a subset of Dact genes. The distribution of functional domains suggests that the ancestral Dact function lied with Wnt signaling, and a role in Tgfβ signaling may have emerged with the Dact2/4 ancestor. Motif reduction, in particular in Dact4, suggests that this protein may counteract the function of the other Dacts. Dact genes were expressed in both distinct and overlapping domains, suggesting possible combinatorial function. Conclusions: The gnathostome Dact gene family comprises four members, derived from a chordate-specific ancestor. The ability to control Wnt signaling seems to be part of the ancestral repertoire of Dact functions, while the ability to inhibit Tgfβ signaling and to carry out specialized, ortholog-specific roles may have evolved later. The complement of Dact genes coexpressed in a tissue provides a complex way to fine-tune Wnt and Tgfβ signaling. Our work provides the basis for future structural and functional studies aimed at unraveling intracellular regulatory networks. [ABSTRACT FROM AUTHOR]

Background: Dact gene family encodes multifunctional proteins that are important modulators of Wnt and TGF-β signaling pathways. Given that these pathways coordinate multiple steps of limb development, we investigated the expression pattern of the two chicken Dact genes ( Dact1 and Dact2) from early limb bud up to stages when several tissues are differentiating. Results: During early limb development (HH24-HH30) Dact1 and Dact2 were mainly expressed in the cartilaginous rudiments of the appendicular skeleton and perichondrium, presenting expression profiles related, but distinct. At later stages of development (HH31-HH35), the main sites of Dact1 and Dact2 expression were the developing synovial joints. In this context, Dact1 expression was shown to co-localize with regions enriched in the nuclear β-catenin protein, such as developing joint capsule and interzone. In contrast, Dact2 expression was restricted to the interzone surrounding the domains of bmpR-1b expression, a TGF-β receptor with crucial roles during digit morphogenesis. Additional sites of Dact expression were the developing tendons and digit blastemas. Conclusions: Our data indicate that Dact genes are good candidates to modulate and, possibly, integrate Wnt and TGF-β signaling during limb development, bringing new and interesting perspectives about the roles of Dact molecules in limb birth defects and human diseases. Developmental Dynamics 243:428-439, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The odo/ apper (Frd) proteins are recently discovered signaling adaptors, which functionally and physically interact with Wnt and Nodal signaling pathways during vertebrate development. The Frd1 and Frd2 genes are expressed in dynamic patterns in early embryos, frequently in cells undergoing epithelial–mesenchymal transition. The Frd proteins function in multiple developmental processes, including mesoderm and neural tissue specification, early morphogenetic cell movements, and organogenesis. Loss-of-function studies using morpholino antisense oligonucleotides demonstrate that the Frd proteins regulate Wnt signal transduction in a context-dependent manner and may be involved in Nodal signaling. The identification of Frd-associated factors and cellular targets of the Frd proteins should shed light on the molecular mechanisms underlying Frd functions in embryonic development and in cancer. [ABSTRACT FROM AUTHOR]

Frodo is a novel conserved regulator of Wnt signaling that has been identified by its association with Dishevelled, an intracellular component of Wnt signal transduction. To understand further how Frodo functions, we have analyzed its role in neural development using specific morpholino antisense oligonucleotides. We show that Frodo and the closely related Dapper synergistically regulate head development and morphogenesis. Both genes were cell-autonomously required for neural tissue formation, as defined by the pan-neural markers sox2 and nrp1. By contrast, β-catenin was not required for pan-neural marker expression, but was involved in the control of the anteroposterior patterning. In the mesoderm, Frodo and Dapper were essential for the expression of the organizer genes chordin, cerberus and Xnr3, but they were not necessary for the expression of siamois and goosecoid, established targets of β-catenin signaling. Embryos depleted of either gone showed a decreased transcriptional response to TCF3-VP16, a β-catenin-independent transcriptional activator. Whereas the C terminus of Frodo binds Dishevelled, we demonstrate that the conserved N-terminal domain associates with TCF3. Based on these observations, we propose that Frodo and Dapper link Dsh and TCF to regulate Wnt target genes in a pathway parallel to that of β-cateuin. [ABSTRACT FROM AUTHOR]

An exhaustive study of the Sam/Frodo family of non-LTR retrotransposons in the Caenorhabditis elegans and Caenorhabditis briggsae genomes demonstrated that C. briggsae contains 60 Sam/Frodo elements including a new subfamily designated Merry, while at least 1000 elements are present in C. elegans. In contrast to C. elegans, C. briggsae does not contain any other non-LTR retrotransposons. The Sam/Frodo/Merry sequences in C. briggsae are shorter and less complete than the Sam/Frodo sequences in C. elegans probably because they all lack a functional first open reading frame (ORF1) and because the genome only encodes one functional reverse transcriptase gene of a non-LTR retrotransposon. Evidence of purifying selection for a functional reverse transcriptase sequence in master/leader elements was found in both nematodes in spite of low copy numbers in C. briggsae. Sam elements in C. elegans are the most abundant Sam/Frodo/Merry family members. They contain the only functional ORF1 copies and, unlike Frodo and Merry members, have a higher GC content than the genomic regions in which they reside. This may indicate a higher transcription rate within this subfamily. [Copyright &y& Elsevier]

Dact/Dapper/Frodo members belong to an evolutionarily conserved family of Dishevelled-binding proteins present in mammals, birds, amphibians and fishes that are involved in the regulation of Wnt and TGF-β signaling. In addition to the three established genes (Dact1-3) that compose the Dact family, a fourth paralogue group of related proteins has been recently identified and named Dact-4. Interestingly, Dact-4 is the most rapidly evolving gene of the entire family, as it displays very low homology with other Dact proteins and has lost key conserved domains. Dact-4 is not present in mammals, but weakly conserved homologs were found in reptiles and fishes. Recent RNAseq from our group identified new genes specifically expressed in the Xenopus laevis Spemann organizer. Among these, LOC1 00170590 mRNA encoded a protein sharing weak homology with a coelacanth Dact-like protein member. Here, by analyzing protein phylogeny and synteny, we show that this organizer gene corresponds to Dact-4. We report that Dact-4 is expressed in the Xenopus blastula pre-organizer region in addition to the gastrula organizer, as well as in placodes, eyes, neural tube, presomitic mesoderm and pronephros. Dact-4-Flag microinjection experiments suggest it is a nucleocytoplasmic protein, as are the other Dact paralogues. [ABSTRACT FROM AUTHOR]