Suchergebnisse

In 1998 the Latin American and the Caribbean countries had to deal with an extremely high degree of volatility in international finance and trade. Considering the strength of the negative external shocks, the region's economies performed reasonably well. This volatility is still in evidence, however, and many of these shocks have a delayed effect. Consequently, the situation at the close of 1998 and the outlook for 1999 remain highly problematic. (ECLAC Notes/DÜI)

Community-engaged research (CER) aspires to co-construct knowledge for action in groups that recognize people's varied expertise and engage in democratic decision making. The CER literature has chronicled these processes in small participatory collectives but is less clear on the strategies or principles that guide collaborative approaches to data analysis in research partnerships that have hundreds of contributors playing distinct roles. The purpose of this paper is to critically assess and describe strategies for co-constructing knowledge with students and teachers who participated in a study that grew out of a broader research–practice partnership. In Part I of our findings, drawing on the concept of prefigurative experiments, we discuss the collaborative practices in our research team that took shape as we prepared data claims to share with students and teachers. In Part II, we discuss sessions interpreting the data with students and teachers in which they conveyed the emotional, embodied, and relational dimensions of student voice experiences. We conclude by discussing how this effort to be accountable to and in relationship with students and teachers, while incomplete on its own, spurred the design of new practices for democratizing data analysis and knowledge production in our research–practice partnership.

Enzymes with a broad substrate specificity are of great interest both at the basic and applied level. Understanding the main parameters that make an enzyme substrate ambiguous could be thus important not only for their selection from the ever-increasing amount of sequencing data but also for engineering a more substrate promiscuous variant. This issue, which remains unresolved, was herein investigated by targeting a serine ester hydrolase (EH102), which exhibits a narrow substrate spectrum, being only capable of hydrolyzing 16 out of 96 esters tested. By using a modeling approach, we demonstrated that one can rationalize active site parameters defining substrate promiscuity, and that based on them the substrate specificity can be significantly altered. This was accomplished by designing two variants, EH102DM2 and EH102TM2, that hydrolyze 51 and 63 esters, respectively, while maintaining similar or higher turnover rates compared to the original enzyme. We hypothesized that the parameters identified here (the volume, size, exposure, enclosure, hydrophobicity, and hydrophilicity of the active site cavity and its tightness) can serve in the future to expand the substrate spectra of esterases and thus expand their use in biotechnology and synthetic chemistry. ; This work was funded by grant 'INMARE' from the European Union's Horizon 2020 (grant agreement no. 634486), grants PCIN-2017-078 (within the Marine Biotechnology ERA-NET), and BIO2017-85522-R and PID2019-106370RB-I00 grants from the Spanish Ministry of Science and Innovation, Ministerio de Economía y Competitividad, Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER) and European Union (EU). This work has also been supported by a predoctoral fellowship from the Spanish Ministry of Science and Innovation (FPU19/00608). ; Peer Reviewed ; Postprint (author's final draft)

Using in-depth interviews, this study examined the social upbringing, subjective experiences and coping mechanisms of Mexican origin ex-convicts before and after their incarceration. Overall, our participants experienced multiple structural disadvantages prior to and following incarceration. Many grew up in environments with little social control—lacking good parenting or role models—and embedded in communities of concentrated poverty and criminality. Many also disclosed their struggles to survive, lack of positive influences and legitimate/constructive coping mechanisms. Contrary to public stereotypes that Mexican origin ex-convicts are hardcore criminals, many were convicted of non-violent drug-related charges and the majority aspired to a crime-free future. To reduce recidivism and minimize future re-offending, we suggest that clinical practitioners, social service providers and policy planners address the aforementioned needs and challenges that contributed to ex-convicts getting in trouble with the law to begin with.

32 p.-4 tab-3 fig.-2 tab. suppl. ; Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-«, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-« gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Design, setting, participants, & measurements Eighty-three patients with early-onset atypical hemolytic uremic syndrome (,2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-«. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Results Four patients carried mutations in diacylglycerol kinase-«, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-« and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-« and C3 mutations. Conclusions Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase-« mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-« and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment. ; Work in this report was funded by Spanish "Ministerio de Economía y Competitividad" Grants SAF2011-26583, PS09/00122 (to M.L.T.), SAF2012-38636 (to M.L.T.), and PI1200597 (to P.S.-C.) and Fundación Renal Inigo Alvarez de Toledo and Seventh Framework ~Programme European Union Project EURenOmics Grant 305608 (to S.R.d.C.). In addition, this work was supported by Autonomous Region of Madrid Grant S2010/BMD-2316 (to M.L.T., P.S.-C., and S.R.d.C.). ; Peer reviewed

Enzyme engineering has allowed not only the de novo creation of active sites catalysing known biological reactions with rates close to diffusion limits, but also the generation of abiological sites performing new-to-nature reactions. However, the catalytic advantages of engineering multiple active sites into a single protein scaffold are yet to be established. Here, we report on proteins with two active sites of biological and/or abiological origin, for improved natural and non-natural catalysis. The approach increased the catalytic properties, such as enzyme efficiency, substrate scope, stereoselectivity and optimal temperature window, of an esterase containing two biological sites. Then, one of the active sites was metamorphosed into a metal-complex chemocatalytic site for oxidation and Friedel–Crafts alkylation reactions, facilitating synergistic chemo- and biocatalysis in a single protein. The transformations of 1-naphthyl acetate into 1,4-naphthoquinone (conversion approx. 100%) and vinyl crotonate and benzene into 3-phenylbutyric acid (≥83%; e.e. >99.9%) were achieved in one pot with this artificial multifunctional metalloenzyme. ; This work was funded by grant 'INMARE' from the European Union's Horizon 2020 (grant agreement no. 634486), grants PCIN-2017-078 (within the Marine Biotechnology ERA-NET), CTQ2016-79138-R, BIO2016-76601-C3-1-R, BIO2016-76601-C3-3-R, BIO2017-85522-R, RTI2018-095166-B-I00 and RTI2018-095090-B-100 from the Ministerio de Economía y Competitividad, the Ministerio de Ciencia, Innovación y Universidades (MCIU), the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and the European Union (EU). P.N.G. and R.B. acknowledge the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant No. BB/M029085/1) and the Centre of Environmental Biotechnology Project and the Supercomputing Wales project, which are partly funded by the European Regional Development Fund (ERDF) through the Welsh Government. The authors gratefully acknowledge the financial support provided by the ERDF. C.C. thanks the Ministerio de Economía y Competitividad and FEDER for a Ph.D. fellowship (Grant BES-2015-073829). J.L.G.-A. thanks the support of the Spanish Ministry of Education, Culture and Sport through the National Program FPU (FPU17/00044). I.C.-R. thanks the Regional Government of Madrid for a fellowship (PEJ_BIO_AI_1201). The authors would like to acknowledge S. Ciordia and M. C. Mena for MALDI-TOF/TOF analysis. We thank the staff of both the European Synchrotron Radiation Facility (ESRF, Grenoble, France), for providing access and technical assistance at beamline ID30A-1/MASSIf-1, and the Synchrotron Radiation Source at Alba (Barcelona, Spain), for assistance at BL13-XALOC beamline. The authors would also like to acknowledge M. J. Vicente and M. A. Pascual at the Servicio Interdepartamental de Investigación (SIDI) of the Autonomous University of Madrid for the ESI-MS analyses.