| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
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| 4. |
- Abrahamson, Magnus, et al.
(författare)
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Cystatins.
- 2003
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Ingår i: Biochemical Society Symposia. - 0067-8694. ; 70, s. 179-199
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Alvarez Fernandez, Marcia, et al.
(författare)
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Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:18, s. 18221-18228
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Tidskriftsartikel (refereegranskat)abstract
- Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared to its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L, and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg26-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5 and 1.8 Å resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel -sheet wrapped around a five-turn -helix. The structures reveal differences in the peptidase-interacting regions when compared to other cystatins, providing plausible explanations to the restricted inhibitory specificity of cystatin D for some papain-like peptidases, and its lack of reactivity towards legumain-related enzymes. This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription.
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| 6. |
- Alvarez Fernandez, Marcia, et al.
(författare)
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Enhancement of sulphide production in anaerobic packed bed bench-scale biofilm reactors by sulphate reducing bacteria
- 2006
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Ingår i: Biotechnology Letters. - : Springer Science and Business Media LLC. - 1573-6776 .- 0141-5492. ; 28:3, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Two biofilm reactors, using pumice stone and Poraver as biofilm supports, were run, based on the optimization of sulphide production using a factorial design. The maximum H2S concentrations reached were 10 and 15 mm, respectively, both being appropriate for metal precipitation in effluents. The set-up of the pumice stone biofilm reactor is suitable for application in the mining area in the Bolivian Andean region, where this material is widely available. The use of specific primers for sulphate-reducing bacteria groups permits the identification of the sulphide-producing bacteria present in biofilms.
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| 7. |
- Alvarez Fernandez, Marcia, et al.
(författare)
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Inhibition of mammalian legumain by some cystatins is due to a novel second reactive site
- 1999
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:27, s. 19195-19203
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the inhibition of the recently identified family C13 cysteine peptidase, pig legumain, by human cystatin C. The cystatin was seen to inhibit enzyme activity by stoichiometric 1:1 binding in competition with substrate. The Ki value for the interaction was 0.20 nM, i.e. cystatin C had an affinity for legumain similar to that for the papain-like family C1 cysteine peptidase, cathepsin B. However, cystatin C variants with alterations in the N-terminal region and the "second hairpin loop" that rendered the cystatin inactive against cathepsin B, still inhibited legumain with Ki values 0.2-0.3 nM. Complexes between cystatin C and papain inhibited legumain activity against benzoyl-Asn-NHPhNO2 as efficiently as did cystatin C alone. Conversely, cystatin C inhibited papain activity against benzoyl-Arg-NHPhNO2 whether or not the cystatin had been incubated with legumain, strongly indicating that the cystatin inhibited the two enzymes with non-overlapping sites. A ternary complex between legumain, cystatin C, and papain was demonstrated by gel filtration supported by immunoblotting. Screening of a panel of cystatin superfamily members showed that type 1 inhibitors (cystatins A and B) and low Mr kininogen (type 3) did not inhibit pig legumain. Of human type 2 cystatins, cystatin D was non-inhibitory, whereas cystatin E/M and cystatin F displayed strong (Ki 0.0016 nM) and relatively weak (Ki 10 nM) affinity for legumain, respectively. Sequence alignments and molecular modeling led to the suggestion that a loop located on the opposite side to the papain-binding surface, between the alpha-helix and the first strand of the main beta-pleated sheet of the cystatin structure, could be involved in legumain binding. This was corroborated by analysis of a cystatin C variant with substitution of the Asn39 residue in this loop (N39K-cystatin C); this variant showed a slight reduction in affinity for cathepsin B (Ki 1.5 nM) but >>5,000-fold lower affinity for legumain (Ki >>1,000 nM) than wild-type cystatin C.
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| 8. |
- Alvarez Fernandez, Marcia
(författare)
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Structural and Functional Studies on Human Type 2 Cystatins
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteolytic enzymes are enzymes that hydrolyze peptide bonds in peptides and proteins. This ability to carry out protein degradation is essential for many cellular and extracellular processes that occur in all living organisms. Cysteine peptidases constitute a class of proteolytic enzymes. Among these, papain-like (C1) peptidases are the mostly studied ones. Inhibitors regulate proteolytic activities in the body. During more that two decades, cystatins have been seen as the natural inhibitors of papain-like peptidases. It has been simple to divide them into three major groups and there have been no larger differences between them when it comes to peptidase binding ability. In this thesis, the finding and characterization of human cystatins E and F are described. These cystatins show signs of adaptation to a more specific function thanks to their restricted localization and structural peculiarities, which are also reflected in their inhibition patterns. They give rise to a new branch of cystatins. In addition to this, the confirmation of the novel cystatin function to act as mammalian legumain (belonging to the C13 family of peptidases) inhibitors, the localization of the binding site and the finding that this feature is only applicable to some cystatins, are also described. These factors revealed that cystatins make up a system more complicated than that believed from the beginning. We were urged to dig deeper into this issue and we found plenty of information in the crystal structure of human cystatin D, which allowed us to follow up the studies on the C1 peptidase binding site, but also to establish the preliminary structural requirements for legumain inhibition by cystatins. These requirements were then confirmed by producing cystatin D variants that do inhibit mammalian legumain. Thus, this thesis work has contributed to a better understanding of the inhibitory ability of type 2 cystatins. The pieces of the cystatin puzzle start to fall into place and give a clearer picture of how such small proteins can be responsible for regulating the activity of such important peptidases in the body.
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| 9. |
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| 10. |
- Ljunggren, Anna, et al.
(författare)
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Crystal Structure of the Parasite Protease Inhibitor Chagasin in Complex with a Host Target Cysteine Protease.
- 2007
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 371:1, s. 137-153
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Tidskriftsartikel (refereegranskat)abstract
- Chagasin is a protein produced by Trypanosoma cruzi, the parasite that causes Chagas' disease. This small protein belongs to a recently defined family of cysteine protease inhibitors. Although resembling well-known inhibitors like the cystatins in size (110 amino acid residues) and function (they all inhibit papain-like (Cl family) proteases), it has a unique amino acid sequence and structure. We have crystallized and solved the structure of chagasin in complex with the host cysteine protease, cathepsin L, at 1.75 angstrom resolution. An inhibitory wedge composed of three loops (L2, L4, and L6) forms a number of contacts responsible for high-affinity binding (K-i, 39 pM) to the enzyme. All three loops interact with the catalytic groove, with the central loop L2 inserted directly into the catalytic center. Loops L4 and L6 embrace the enzyme molecule from both sides and exhibit distinctly different patterns of protein-protein recognition. Comparison with a 1.7 angstrom structure of uncomplexed chagasin, also determined in this study, demonstrates that a conformational change of the first binding loop (1-4) allows extended binding to the non-primed substrate pockets of the enzyme active site cleft, thereby providing a substantial part of the inhibitory surface. The mode of chagasin binding is generally similar, albeit distinctly different in detail, when compared to those displayed by cystatins and the cysteine protease inhibitory p41 fragment of the invariant chain. The chagasin-cathepsin L complex structure provides details of how the parasite protein inhibits a host enzyme of possible importance in host defense. The high level of structural and functional similarity between cathepsin L and the T cruzi enzyme cruzipain gives clues to how the cysteine protease activity of the parasite can be targeted. This information will aid in the development of synthetic inhibitors for use as potential drugs for the treatment of Chagas disease.
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