Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (
Uren et al., 2000
). Like caspases, meta- and paracaspases are multifunctional ...proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis and programmed cell death. The broad phylogenetic distribution of meta- and paracaspases across all kingdoms of life and large variation of their biochemical and structural features complicate classification and annotation of the rapidly growing number of identified homologs. Establishment of an adequate classification and unified nomenclature of meta- and paracaspases is especially important to avoid frequent confusion of these proteases with caspases - a tenacious misnomer that unfortunately does not appear to decline with time. This letter represents a consensus opinion of researchers studying different aspects of caspases, meta- and paracaspases in various organisms, ranging from microbes to plants and animals.
The lysosomal cysteine proteases cathepsins S and L play crucial roles in the degradation of the invariant chain during maturation of MHC class II molecules and antigen processing. The p41 form of ...the invariant chain includes a fragment which specifically inhibits cathepsin L but not S. The crystal structure of the p41 fragment, a homologue of the thyroglobulin type‐1 domains, has been determined at 2.0 Å resolution in complex with cathepsin L. The structure of the p41 fragment demonstrates a novel fold, consisting of two subdomains, each stabilized by disulfide bridges. The first subdomain is an α‐helix–β‐strand arrangement, whereas the second subdomain has a predominantly β‐strand arrangement. The wedge shape and three‐loop arrangement of the p41 fragment bound to the active site cleft of cathepsin L are reminiscent of the inhibitory edge of cystatins, thus demonstrating the first example of convergent evolution observed in cysteine protease inhibitors. However, the different fold of the p41 fragment results in additional contacts with the top of the R‐domain of the enzymes, which defines the specificity‐determining S2 and S1′ substrate‐binding sites. This enables inhibitors based on the thyroglobulin type‐1 domain fold, in contrast to the rather non‐selective cystatins, to exhibit specificity for their target enzymes.
Cathepsin X is a widespread, abundantly expressed papain-like mammalian lysosomal cysteine protease. It exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity and shares a similar ...activity profile with cathepsin B. The latter has been implicated in normal physiological events as well as in various pathological states such as rheumatoid arthritis, Alzheimer's disease and cancer progression. Thus the question is raised as to which of the two enzyme activities has actually been monitored.
The crystal structure of human cathepsin X has been determined at 2.67 A resolution. The structure shares the common features of a papain-like enzyme fold, but with a unique active site. The most pronounced feature of the cathepsin X structure is the mini-loop that includes a short three-residue insertion protruding into the active site of the protease. The residue Tyr27 on one side of the loop forms the surface of the S1 substrate-binding site, and His23 on the other side modulates both carboxy-monopeptidase as well as carboxy-dipeptidase activity of the enzyme by binding the C-terminal carboxyl group of a substrate in two different sidechain conformations.
The structure of cathepsin X exhibits a binding surface that will assist in the design of specific inhibitors of cathepsin X as well as of cathepsin B and thereby help to clarify the physiological roles of both proteases.
Abstract Retinitis as a feature of syphilitic uveitis in immunocompromised individuals is a common finding. We present spectral domain OCT images of early syphilitic retinitis pre and post treatment ...with penicillin. This case suggests that the inner retinal layers may be selectively involved with early syphilitic retinitis. Early treatment is important to avoid outer layer retinal involvement and to decrease ocular morbidity.
Cathepsin X, purified to homogeneity from human liver, is a single chain glycoprotein with a molecular mass of ≈ 33 kDa and pI 5.1–5.3. Cathepsin X was inhibited by stefin A, cystatin C and chicken ...cystatin (Ki = 1.7–15.0 nm), but poorly or not at all by stefin B (Ki > 250 nm) and l‐kininogen, respectively. The enzyme was also inhibited by two specific synthetic cathepsin B inhibitors, CA‐074 and GFG‐semicarbazone. Cathepsin X was similar to cathepsin B and found to be a carboxypeptidase with preference for a positively charged Arg in P1 position. Contrary to the preference of cathepsin B, cathepsin X normally acts as a carboxymonopeptidase. However, the preference for Arg in the P1 position is so strong that cathepsin X cleaves substrates with Arg in antepenultimate position, acting also as a carboxydipeptidase. A large hydrophobic residue such as Trp is preferred in the P1′ position, although the enzyme cleaved all P1′ residues investigated (Trp, Phe, Ala, Arg, Pro). Cathepsin X also cleaved substrates with amide‐blocked C‐terminal carboxyl group with rates similar to those of the unblocked substrates. In contrast, no endopeptidase activity of cathepsin X could be detected on a series of o‐aminobenzoic acid‐peptidyl‐N‐2,‐dinitrophenylethylenediamine substrates. Furthermore, the standard cysteine protease methylcoumarine amide substrates (kcat/Km≈ 5.0 × 103 m−1·s−1) were degraded ≈ 25‐fold less efficiently than the carboxypeptidase substrates (kcat/Km ≈ 120.0 × 103 m−1·s−1).
Enhancing parental involvement is a major concern for policymakers in education in many countries. Literature review has exposed strong connections between parental involvements in school activities ...and student outcomes (also achievements). For exploring the association between parental involvement in school activities and student reading achievement, we used data from the latest cycle of the Progress in International Reading Literacy Study (PIRLS 2011) conducted by the International Association for the Evaluation of Educational Achievement (IEA). The study assesses reading literacy at Grade 4 using representative samples of students in the participating education systems. PIRLS also collects extensive, internationally comparable information on the background characteristics of the students, their parents, teachers and the schools where they study. We conducted the analyses utilizing information on parental involvement in school activities (as reported by school principals), parental level of education (as reported by parents), and student reading achievement (PIRLS achievement scores). We used data from 54 of 56 education systems that included all relevant data needed for the analyses. Regarding that, this paper seeks to answer two questions. First, is there a relationship between parental involvement in school activities and student reading achievement in the education systems participating in PIRLS 2011? Given that both parental involvement and student achievement are often influenced by the family socio-economic context, the second question is whether parental involvement is associated with the level of parental education within each of the analysed education systems? This paper presents evidence demonstrating that within most of the 54 education systems we analysed, parental involvement in school activities is positively associated with student performance in PIRLS 2011. That is to say, students enrolled in schools with higher parental involvement tend to have higher reading achievement. It also shows that the level of parental involvement in school is positively associated with the level of parental education. Thus, parents with lower education levels are likely to participate less in school and vice versa. The conclusions suggest that the promotion of parental involvement may be an effective strategy for increasing reading achievement, and policies in this direction are particularly relevant for schools with students whose parents have lower levels of education.
Enhancing parental involvement is a major concern for policymakers in education in many countries. Literature review has exposed strong connections between parental involvements in school activities ...and student outcomes (also achievements). For exploring the association between parental involvement in school activities and student reading achievement, we used data from the latest cycle of the Progress in International Reading Literacy Study (PIRLS 2011) conducted by the International Association for the Evaluation of Educational Achievement (IEA). The study assesses reading literacy at Grade 4 using representative samples of students in the participating education systems. PIRLS also collects extensive, internationally comparable information on the background characteristics of the students, their parents, teachers and the schools where they study. We conducted the analyses utilizing information on parental involvement in school activities (as reported by school principals), parental level of education (as reported by parents), and student reading achievement (PIRLS achievement scores). We used data from 54 of 56 education systems that included all relevant data needed for the analyses. Regarding that, this paper seeks to answer two questions. First, is there a relationship between parental involvement in school activities and student reading achievement in the education systems participating in PIRLS 2011? Given that both parental involvement and student achievement are often influenced by the family socio-economic context, the second question is whether parental involvement is associated with the level of parental education within each of the analysed education systems? This paper presents evidence demonstrating that within most of the 54 education systems we analysed, parental involvement in school activities is positively associated with student performance in PIRLS 2011. That is to say, students enrolled in schools with higher parental involvement tend to have higher reading achievement. It also shows that the level of parental involvement in school is positively associated with the level of parental education. Thus, parents with lower education levels are likely to participate less in school and vice versa. The conclusions suggest that the promotion of parental involvement may be an effective strategy for increasing reading achievement, and policies in this direction are particularly relevant for schools with students whose parents have lower levels of education. Adapted from the source document.
Retinitis as a feature of syphilitic uveitis in immunocompromised individuals is a common finding. We present spectral domain OCT images of early syphilitic retinitis pre and post treatment with ...penicillin. This case suggests that the inner retinal layers may be selectively involved with early syphilitic retinitis. Early treatment is important to avoid outer layer retinal involvement and to decrease ocular morbidity.
Es frecuente el hallazgo de la retinitis como una característica de uveítis sifilítica en personas inmunodeprimidas. Presentamos imágenes de OCT Spectral Domain de retinitis sifilítica incipiente antes y después del tratamiento con penicilina. Este caso sugiere que las capas internas de la retina pueden estar afectadas selectivamente por retinitis sifilítica incipiente. Es importante llevar a cabo un tratamiento temprano para evitar la afectación de la capa externa de la retina y para reducir la morbilidad ocular.
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