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Aviles, J.

Publications and source records attributed to Aviles, J..

4 recordsLinked to original sources

Multidomain Coupling Governs FoxP1 Assembly and Nuclear Compartmentalization

FoxP1 is a multidomain transcription factor implicated in development, immunity, and cancer, widely proposed to function as a dimer. However, the molecular mechanisms governing its assembly and nuclear organization in living cells remain unclear. Here, we combine biochemical assays and live-cell fluorescence lifetime imaging to resolve FoxP1 homotypic interactions. We show that FoxP1 forms heterogeneous complexes whose stability is governed by antagonistic coupling between its leucine-zipper (ZIP) and Forkhead (FKH) domains. The FoxP1 ZIP domain promotes dimerization while suppressing FKH-mediated interactions, revealing a competing interdomain mechanism that tunes complex formation. Pathogenic and deletion variants disrupt this intricate balance, altering interaction stability and promoting the formation of dense nuclear condensates upon loss of DNA binding. Together, our results demonstrate that FoxP1 assembly is encoded by its multidomain architecture. Our findings show how competing interaction domains regulate transcription factor complex formation, nuclear organization, and DNA binding, with implications for disease-associated dysregulation. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=85 SRC="FIGDIR/small/728184v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@bb8cbcorg.highwire.dtl.DTLVardef@1149339org.highwire.dtl.DTLVardef@1cd87d7org.highwire.dtl.DTLVardef@9147a4_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIFoxP1 complexes assemble through two distinct mechanisms mediated by the FKH and ZIP domains. C_LIO_LIInterdomain coupling switches the configuration of the FoxP1 complex. C_LIO_LIFKH-mediated FoxP1 oligomers and other higher-order complexes accumulate at the nuclear periphery, whereas ZIP-mediated dimers remain more uniformly distributed. C_LIO_LIDisruption of FKH-DNA binding drives formation of protein-dense FoxP1 condensates. C_LI

biophysics↗

MPNN-guided redesign of PET hydrolases with enhanced catalytic activity below the PET glass transition temperature

Enzymatic depolymerization of polyethylene terephthalate (PET) presents a sustainable route for plastic circularity, but its industrial viability is disadvantaged by the need for thermostable enzymes active under mild, energy-efficient conditions. While Polyester Hydrolase Leipzig 7 (PHL7, also known as PES-H1) rapidly degrades amorphous PET near the glass transition temperature of this polymer (~65{degrees}C), its poor protein expression, inactivation above 60{degrees}C and slow depolymerization below 60{degrees}C limits its practical application. Here, we employ ProteinMPNN and LigandMPNN, structural and evolutionary information, to redesign the sequence of PHL7 and improve protein expression, thermostability and activity. We identified 2/36 experimentally tested variants (D5, D11) with enhanced PET depolymerization at 50{degrees}C, achieving the same efficiency as PHL7 at 70{degrees}C but with a shifted product profile, favoring mono-(2-hydroxyethyl) terephthalate (MHET) over terephthalate. Molecular dynamics revealed that these redesigns exhibit enhanced flexibility in active site regions, providing a mechanistic understanding of their low-temperature catalysis. These variants enable a potential route to resynthesize virgin PET via MHET polycondensation, offering an efficient circular economy pathway.

bioengineering↗

Priming of C-glycoside flavones in Colobanthus quitensis with salicylic acid, methyl jasmonate, pimelic acid, suberic acid, and azelaic acid elicits antifungal activity against Botrytis cinerea

Colobanthus quitensis, one of only two native angiosperms in Antarctica, produces C-glycosyl flavones with antifungal activity against Botrytis cinerea. In this study, the exogenous application of the elicitors salicylic acid (SA), methyl jasmonate (MeJA), pimelic acid (PA), suberic acid (SuA), and azelaic acid (AzA) was evaluated for their effect on the accumulation of bioactive metabolites in in vitro-cultivated plants. Exposure to these compounds significantly modulated the expression of key genes in the phenylpropanoid and flavonoid pathways, including pal, chs, chi, fnsII, as well as regulatory genes such as myb12, bhlh, and wrky33, enhancing PAL activity and the accumulation of schaftoside, neoschaftoside, saponarin, and swertiajaponin. This priming process improved the antifungal activity of the extracts, with MeJA and PA identified as the most effective treatments. The in vitro culture approach enabled the assessment of a protected and hard-to-access species without the need for wild harvesting. These results suggest that the exogenous application of elicitors constitutes an efficient strategy to modulate the biosynthesis of specialised metabolites, with implications for the development of biocontrol agents and the improvement of efficiency in sustainable agricultural systems. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/646165v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@67f8corg.highwire.dtl.DTLVardef@9ff3a1org.highwire.dtl.DTLVardef@13403aaorg.highwire.dtl.DTLVardef@1dc95b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

Open Educational Resources for distributed hands-on teaching in molecular biology

The urgent need to develop a more equitable bioeconomy has positioned biotechnology capacity building at the forefront of international priorities. However, in many educational institutions, particularly in low-and middle-income countries, this remains a major challenge due to limited access to reagents, equipment, and technical documentation. In this work, we describe Open Educational Resources (OER) composed of locally produced biological reagents, open source hardware and free software to teach fundamental techniques in biotechnology such as LAMP DNA amplification, RT-PCR RNA detection, enzyme kinetics and fluorescence imaging. The use of locally produced reagents and devices reduces costs by up to one order of magnitude. During the pandemic lockdowns, these tools were distributed nationwide to students homes as a lab-in-a-box for remote teaching of molecular biology. To test their performance, a total of 93 undergraduate students tested these resources during a biochemistry practical course. 27 out of 31 groups ([~]87%) successfully achieved the objectives of the PCR activity, while 28 out of 31 groups ([~]90%) correctly identified the target using LAMP reactions. To assess the potential application in secondary school, we organized three workshops for high school teachers from different institutions across Chile and performed an anonymous questionnaire, obtaining a strong agreement on how these OER broaden teachers perspectives on the techniques and facilitate the teaching of molecular biology topics. This effort was made possible through a close collaboration with open source technology advocates and members of DIYbio communities, whose work is paving the way for low-cost training in biology. All the protocols and design files are available under open source licenses.

molecular biology↗