Activin Receptor Type 2A (ACVR2A) Functions Directly in Osteoblasts as a Negative Regulator of Bone Mass

Bone and skeletal muscle mass are highly correlated in mammals, suggesting the existence of common anabolic signaling networks that coordinate the development of these two anatomically adjacent tissues. The activin signaling pathway is an attractive candidate to fulfill such a role. Here, we generated mice with conditional deletion of activin receptor (ACVR) type 2A, ACVR2B, or both, in osteoblasts, to determine the contribution of activin receptor signaling in regulating bone mass. Immunohistochemistry localized ACVR2A and ACVR2B to osteoblasts and osteocytes. Primary osteoblasts expressed activin signaling components, including ACVR2A, ACVR2B, and ACVR1B (ALK4) and demonstrated increased levels of phosphorylated Smad2/3 upon exposure to activin ligands. Osteoblasts lacking ACVR2B did not show significant changes in vitro. However, osteoblasts deficient in ACVR2A exhibited enhanced differentiation indicated by alkaline phosphatase activity, mineral deposition, and transcriptional expression of osterix, osteocalcin, and dentin matrix acidic phosphoprotein 1. To investigate activin signaling in osteoblasts in vivo, we analyzed the skeletal phenotypes of mice lacking these receptors in osteoblasts and osteocytes (osteocalcin-Cre). Similar to the lack of effect in vitro, ACVR2B-deficient mice demonstrated no significant change in any bone parameter. By contrast, mice lacking ACVR2A had significantly increased femoral trabecular bone volume at 6 weeks of age. Moreover, mutant mice lacking both ACVR2A and ACVR2B demonstrated sustained increases in trabecular bone volume, similar to those in ACVR2A single mutants, at 6 and 12 weeks of age. Taken together, these results indicate that activin receptor signaling, predominantly through ACVR2A, directly and negatively regulates bone mass in osteoblasts

Response of different PTH assays to therapy with sevelamer or CaCO3 and active vitamin D sterols

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels

Ideal Interpolation, H-Bases and Symmetry

International audienceMultivariate Lagrange and Hermite interpolation are examples ofideal interpolation. More generally an ideal interpolation problemis defined by a set of linear forms, on the polynomial ring, whosekernels intersect into an ideal.For an ideal interpolation problem with symmetry, we addressthe simultaneous computation of a symmetry adapted basis of theleast interpolation space and the symmetry adapted H-basis ofthe ideal. Beside its manifest presence in the output, symmetry isexploited computationally at all stages of the algorithm

Algebraic Cryptanalysis of STARK-Friendly Designs:Application to MARVELlous and MiMC

The block cipher Jarvis and the hash function Friday, both members of the MARVELlous family of cryptographic primitives, are among the first proposed solutions to the problem of designing symmetric-key algorithms suitable for transparent, post-quantum secure zero-knowledge proof systems such as ZK-STARKs. In this paper we describe an algebraic cryptanalysis of Jarvis and Friday and show that the proposed number of rounds is not sufficient to provide adequate security. In Jarvis, the round function is obtained by combining a finite field inversion, a full-degree affine permutation polynomial and a key addition. Yet we show that even though the high degree of the affine polynomial may prevent some algebraic attacks (as claimed by the designers), the particular algebraic properties of the round function make both Jarvis and Friday vulnerable to Gröbner basis attacks. We also consider MiMC, a block cipher similar in structure to Jarvis. However, this cipher proves to be resistant against our proposed attack strategy. Still, our successful cryptanalysis of Jarvis and Friday does illustrate that block cipher designs for “algebraic platforms” such as STARKs, FHE or MPC may be particularly vulnerable to algebraic attacks

LLANO DE LOS JUNCOS. TEJEDA [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Reflexões sobre as roças em São Tomé e Príncipe

O artigo tem como objetivo apresentar elementos constitutivos da história de São Tomé e Príncipe, segundo menor país do continente africano, que tem como língua oficial o português. Diversas leituras e dados coligidos auxiliaram na redação do texto, que define e contextualiza o universo do sistema latifundiário colonial construído nas duas ilhas e apresenta escolhas políticas e sociais realizadas em função desse sistema ao longo de sua história

\u2018On a nos mots \ue0 dire\u2019. Kanak women\u2019s experience of bridewealth in Lifou

L'articolo \ue8 incentrato sullla bridewealth contestualizzata all'interno delle pratiche e rituali che costituscono l'itinerario che si conclude col matrimonio nella societ\ue0 kanak di Lifou. L'articolo si inserisce nel dibattito contemporaneo sul significato della ricchezza della sposa nella regione e sulla necessit\ue0 di nominare queste pratiche rimanendo aderenti ai modi e espressioni locali.. Bridewealth in Lifou cannot be discussed on its own; rather it should be considered within the plurality of ceremonial acts which are needed to legitimize a marriage as customary. What do these transactions mean? Where does women\u2019s agency lie? Through a longitudinal analysis of ethnographic materials from my fieldwork in Lifou, Loyalty Islands, I consider how Kanak women are engaged in and perceive these ceremonial and cultural processes through a declared women\u2019s perspective that highlights their ability to make autonomous choices in an open ended historical context. I argue that it is a case of \u2018positive agency\u2019. I emphasize that local categories (june hmala and wenehleng) which define specific moments in this process can be subsumed under the anthropological term \u2018bridewealth\u2019. Further, I examine the meaning of money in bridewealth and the fact that the monetary contribution keeps increasing, raising local concerns about the need to regulate the amount circulating in marriage exchanges and its dispersion. Furthermore in Lifou there is no indication that the assembling of the bridewealth by the grooms implies a commoditization and (later) exploitation of women