3D models related to the publication: Comparative anatomy and phylogenetic contribution of intracranial osseous canals and cavities in armadillos and glyptodonts (Xenarthra, Cingulata)

INTRODUCTION: The phylogeny of the Cingulata has been debated in morphological analyses for a long time (Engelmann, 1985; Gaudin &Wible, 2006; Billet et al., 2011; Delsuc et al., 2016; Mitchell et al., 2016; Herrera et al., 2017) and this incongruence was enriched by the contribution of recent molecular analyses (Delsuc et al., 2016; Mitchell et al., 2016). This is particularly the case for the emblematic group of glyptodonts whose mitochondrial genome was recently assembled (Delsuc et al., 2016; Mitchell et al., 2016). Although the cranial anatomy is relatively well known in xenarthrans, their internal cranial anatomy remains poorly studied. Yet, several studies have shown that their exploration provides systematic interest on their past and present diversity (Zurita et al., 2011; Fernicola et al., 2012; Billet et al., 2015; Tambusso & Fari˜na, 2015a; Tambusso & Fari˜na, 2015b; Billet et al., 2017; Boscaini et al., 2018; Boscaini et al., 2020; Tambusso et al., 2021). In a recent study (Le Verger et al., 2021), we describe and compare 8 cranial canals (involved in the vascularization and innervation of the cranium) and alveolar cavities (Figure 1) of 30 specimens belonging to the Cingulata. In this sampling, all extant subfamilies are represented and several large fossil groups including giant forms such as pampatheres and glyptodonts are represented. For the latter, the oldest complete crania have been studied. A sloth and an anteater were also added to the sample as outgroup. Of the total sample, 3D models of 13 specimens are made available (Table 1). The rest of the specimens are available only upon request from LGR. In this study (Le Verger et al., 2021), we present the comparativ investigation of these intracranial osseous canals and alveolar cavities using X-ray microtomography. Their 3D virtual reconstruction enabled us to compare the locations, trajectories, and shape of each homologous structure and discuss their potential interest for cingulate systematics

Cancer epithelia-derived mitochondrial DNA is a targetable initiator of a paracrine signaling loop that confers taxane resistance.

Stromal-epithelial interactions dictate cancer progression and therapeutic response. Prostate cancer (PCa) cells were identified to secrete greater concentration of mitochondrial DNA (mtDNA) compared to noncancer epithelia. Based on the recognized coevolution of cancer-associated fibroblasts (CAF) with tumor progression, we tested the role of cancer-derived mtDNA in a mechanism of paracrine signaling. We found that prostatic CAF expressed DEC205, which was not expressed by normal tissue-associated fibroblasts. DEC205 is a transmembrane protein that bound mtDNA and contributed to pattern recognition by Toll-like receptor 9 (TLR9). Complement C3 was the dominant gene targeted by TLR9-induced NF-κB signaling in CAF. The subsequent maturation complement C3 maturation to anaphylatoxin C3a was dependent on PCa epithelial inhibition of catalase in CAF. In a syngeneic tissue recombination model of PCa and associated fibroblast, the antagonism of the C3a receptor and the fibroblastic knockout of TLR9 similarly resulted in immune suppression with a significant reduction in tumor progression, compared to saline-treated tumors associated with wild-type prostatic fibroblasts. Interestingly, docetaxel, a common therapy for advanced PCa, further promoted mtDNA secretion in cultured epithelia, mice, and PCa patients. The antiapoptotic signaling downstream of anaphylatoxin C3a signaling in tumor cells contributed to docetaxel resistance. The inhibition of C3a receptor sensitized PCa epithelia to docetaxel in a synergistic manner. Tumor models of human PCa epithelia with CAF expanded similarly in mice in the presence or absence of docetaxel. The combination therapy of docetaxel and C3 receptor antagonist disrupted the mtDNA/C3a paracrine loop and restored docetaxel sensitivity

Heterogeneous cancer-associated fibroblast population potentiates neuroendocrine differentiation and castrate resistance in a CD105-dependent manner.

Heterogeneous prostatic carcinoma-associated fibroblasts (CAF) contribute to tumor progression and resistance to androgen signaling deprivation therapy (ADT). CAF subjected to extended passaging, compared to low passage CAF, were found to lose tumor expansion potential and heterogeneity. Cell surface endoglin (CD105), known to be expressed on proliferative endothelia and mesenchymal stem cells, was diminished in high passage CAF. RNA-sequencing revealed SFRP1 to be distinctly expressed by tumor-inductive CAF, which was further demonstrated to occur in a CD105-dependent manner. Moreover, ADT resulted in further expansion of the CD105+ fibroblastic population and downstream SFRP1 in 3-dimensional cultures and patient-derived xenograft tissues. In patients, CD105+ fibroblasts were found to circumscribe epithelia with neuroendocrine differentiation. CAF-derived SFRP1, driven by CD105 signaling, was necessary and sufficient to induce prostate cancer neuroendocrine differentiation in a paracrine manner. A partially humanized CD105 neutralizing antibody, TRC105, inhibited fibroblastic SFRP1 expression and epithelial neuroendocrine differentiation. In a novel synthetic lethality paradigm, we found that simultaneously targeting the epithelia and its microenvironment with ADT and TRC105, respectively, reduced castrate-resistant tumor progression, in a model where either ADT or TRC105 alone had little effect

Pervasive cranial allometry at different anatomical scales and variational levels in extant armadillos

Allometry, i.e., morphological variation correlated with size, is a major pattern in organismal evolution. Since size varies both within and among species, allometry occurs at different variational levels. However, the variability of allometric patterns across levels is poorly known since its evaluation requires extensive comparative studies. Here, we implemented a 3D geometric morphometric approach to investigate cranial allometry at three main variational levels—static, ontogenetic, and evolutionary—and two anatomical scales—entire cranium and cranial subunits—based on a dense intra- and interspecific sampling of extant armadillo diversity. While allometric trajectories differ among distantly related species, they hardly do so among sister families. This suggests that phylogenetic distance plays an important role in explaining allometric divergences. Beyond trajectories, our analyses revealed pervasive allometric shape changes shared across variational levels and anatomical scales. At the entire cranial scale, craniofacial allometry (relative snout elongation and braincase reduction) is accompanied notably by variations of nuchal crests and postorbital constriction. Among cranial subunits, the distribution of allometry was highly heterogeneous, with the frontal and petrosal bones showing the most pervasive shape changes, some of which were undetected at a more global scale. Evidence of widespread and superimposed allometric variations raises questions on their determinants and anatomical correlates and demonstrates the critical role of allometry in morphological evolution

Potential sites of CFTR activation by tyrosine kinases

The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity is also regulated by tyrosine kinases, however the tyrosine phosphorylation sites remain to be identified. In this study we examined 2 candidate tyrosine residues near the boundary between the first nucleotide binding domain and the R domain, a region which is important for channel function but devoid of PKA consensus sequences. Mutating tyrosines at positions 625 and 627 dramatically reduced responses to Src or Pyk2 without altering the activation by PKA, suggesting they may contribute to CFTR regulation

Cube Testers and Key Recovery Attacks On Reduced-Round MD6 and Trivium

CRYPTO 2008 saw the introduction of the hash function MD6 and of cube attacks, a type of algebraic attack applicable to cryptographic functions having a low-degree algebraic normal form over GF(2). This paper applies cube attacks to reduced round MD6, finding the full 128-bit key of a 14-round MD6 with complexity 2^22 (which takes less than a minute on a single PC). This is the best key recovery attack announced so far for MD6. We then introduce a new class of attacks called cube testers, based on efficient property-testing algorithms, and apply them to MD6 and to the stream cipher Trivium. Unlike the standard cube attacks, cube testers detect nonrandom behavior rather than performing key extraction, but they can also attack cryptographic schemes described by nonrandom polynomials of relatively high degree. Applied to MD6, cube testers detect nonrandomness over 18 rounds in 2^17 complexity; applied to a slightly modified version of the MD6 compression function, they can distinguish 66 rounds from random in 2^24 complexity. Cube testers give distinguishers on Trivium reduced to 790 rounds from random with 2^30 complexity and detect nonrandomness over 885 rounds in 2^27, improving on the original 767-round cube attack