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61.
Stijn van Eesbeek Jurriaan H. de Groot Frans C.T. van der Helm Erwin de Vlugt 《Journal of biomechanics》2010,43(13):2539-2547
Short-range stiffness (SRS) is a mechanical property of muscles that is characterized by a disproportionally high stiffness within a short length range during both lengthening and shortening movements. SRS is attributed to the cross-bridges and is beneficial for stabilizing a joint during, e.g., postural conditions. Thus far, SRS has been estimated mainly on isolated mammalian muscles. In this study we presented a method to estimate SRS in vivo in the human wrist joint.SRS was estimated at joint level in the angular domain (N m/rad) for both flexion and extension rotations of the human wrist in nine healthy subjects. Wrist rotations of 0.15 rad at 3 rad/s were imposed at eight levels of voluntary contraction ranging from 0 to 2.1 N m by means of a single axis manipulator.Flexion and extension SRS of the wrist joint was estimated consistently and accurately using a dynamic nonlinear model that was fitted onto the recorded wrist torque. SRS increased monotonically with torque in a way consistent with previous studies on isolated muscles.It is concluded that in vivo measurement of joint SRS represents the population of coupled cross-bridges in wrist flexor and extensor muscles. In its current form, the presented technique can be used for clinical applications in many neurological and muscular diseases where altered joint torque and (dissociated) joint stiffness are important clinical parameters. 相似文献
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Despite the presence of high nutrient concentrations, most ponds located around Brussels (Belgium) show a considerable variation
in turbidity. The importance of submerged macrophytes in maintaining the clear-water state requires identification of the
main factors determining macrophyte abundance and diversity in ponds and small lakes. In this study, the inter-relationships
between submerged macrophyte cover, fish abundance and turbidity were investigated in 13 eutrophic peri-urban ponds. Along
a turbidity gradient, vegetation switched from dominance by Stoneworts (Chara and Nitella spp.) in the clearest ponds, to dominance by Potamogeton pectinatus in ponds with a slightly lower water transparency. Despite the presence of both P. pectinatus and Stoneworts in each of the vegetated ponds, only one became dominant. Only a very low abundance (around 20%) of submerged
vegetation was found in ponds of intermediate turbidity, while macrophytes were absent in turbid ponds. Multi- and univariate
analysis showed a marked difference in chemical, physical and biological properties between ponds deliberately used for fish
stocking and ponds that were not. Macrophyte cover was significantly negatively correlated with turbidity and plankti-benthivorous
fish abundance. No such correlation was observed with piscivorous fish abundance, except for pike that were associated with
a charophyte vegetation in the study ponds. The strong relationship found between fish abundance and turbidity, its negative
effect on submerged vegetation cover, and the importance of submerged vegetation in controlling phytoplankton abundance, should
be taken into account when selecting ponds for fish stocking. It also suggests that the study ponds have a good potential
for ecological quality restoration by biomanipulation. 相似文献
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Caroline M.W. van Stijn Lonneke Vervelde Richard D. Cummings Boris Tefsen 《International journal for parasitology》2010,40(2):215-222
Lambs vaccinated with Haemonchus contortus excretory/secretory (ES) glycoproteins in combination with the adjuvant Alhydrogel are protected against H. contortus challenge infection. Using glycan micro-array analysis we showed that serum from such vaccinated lambs contains IgG antibodies that recognise the glycan antigen Galα1-3GalNAc-R and GalNAcβ1-4(Fucα1-3)GlcNAc-R. Our studies revealed that H. contortus glycoproteins contain Galα1-3Gal-R as well as significant levels of Galα1-3GalNAc-R, which has not been previously reported. Extracts from H. contortus adult worms contain a galactosyltransferase acting on glycan substrates with a terminal GalNAc, indicating that the worms possess the enzymatic potential to synthesise terminal Gal-GalNAc moieties. These data illustrate that glycan micro-arrays constitute a promising technology for fast and specific analysis of serum anti-glycan antibodies in vaccination studies. In addition, this approach facilitates the discovery of novel, antigenic parasite glycan antigens that may have potential for developing glycoconjugate vaccines or utilization in diagnostics. 相似文献
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Ole Lagatie Emmanuel Njumbe Ediage Dirk Van Roosbroeck Stijn Van Asten Ann Verheyen Linda Batsa Debrah Alex Debrah Maurice R. Odiere Ruben TKindt Emmie Dumont Koen Sandra Lieve Dillen Tom Verhaeghe Rob Vreeken Filip Cuyckens Lieven J. Stuyver 《PLoS neglected tropical diseases》2021,15(11)
The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated. 相似文献
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Benno Verbelen Tiziana Girardi Sergey O. Sulima Stijn Vereecke Paulien Verstraete Jelle Verbeeck Jonathan Royaert Sonia Cinque Lorenzo Montanaro Marianna Penzo Maya Imbrechts Nick Geukens Thomas Geuens Koen Dierckx Daniele Pepe Kim Kampen Kim De Keersmaecker 《Engineering in Life Science》2022,22(2):100
Mammalian cells are commonly used to produce recombinant protein therapeutics, but suffer from a high cost per mg of protein produced. There is therefore great interest in improving protein yields to reduce production cost. We present an entirely novel approach to reach this goal through direct engineering of the cellular translation machinery by introducing the R98S point mutation in the catalytically essential ribosomal protein L10 (RPL10‐R98S). Our data support that RPL10‐R98S enhances translation levels and fidelity and reduces proteasomal activity in lymphoid Ba/F3 and Jurkat cell models. In HEK293T cells cultured in chemically defined medium, knock‐in of RPL10‐R98S was associated with a 1.7‐ to 2.5‐fold increased production of four transiently expressed recombinant proteins and 1.7‐fold for one out of two stably expressed proteins. In CHO‐S cells, eGFP reached a 2‐fold increased expression under stable but not transient conditions, but there was no production benefit for monoclonal antibodies. The RPL10‐R98S associated production gain thus depends on culture conditions, cell type, and the nature of the expressed protein. Our study demonstrates the potential for using a ribosomal protein mutation for pharmaceutical protein production gains, and further research on how various factors influence RPL10‐R98S phenotypes can maximize its exploitability for the mammalian protein production industry. 相似文献
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The proteasome-interacting protein Rad23 is a long-lived protein. Interaction between Rad23 and the proteasome is required for Rad23's functions in nucleotide excision repair and ubiquitin-dependent degradation. Here, we show that the ubiquitin-associated (UBA)-2 domain of yeast Rad23 is a cis-acting, transferable stabilization signal that protects Rad23 from proteasomal degradation. Disruption of the UBA2 domain converts Rad23 into a short-lived protein that is targeted for degradation through its N-terminal ubiquitin-like domain. UBA2-dependent stabilization is required for Rad23 function because a yeast strain expressing a mutant Rad23 that lacks a functional UBA2 domain shows increased sensitivity to UV light and, in the absence of Rpn10, severe growth defects. The C-terminal UBA domains of Dsk2, Ddi1, Ede1, and the human Rad23 homolog hHR23A have similar protective activities. Thus, the UBA2 domain of Rad23 is an evolutionarily conserved stabilization signal that allows Rad23 to interact with the proteasome without facing destruction. 相似文献