Trans-complex education as a strategy in pandemic and post-pandemic COVID-19

The trans-complex approach to education changes the work of the teacher and faculty, in particular the social outlook and resilience of the student is tested with this new mode of self-learning and adaptation. The new proposed form of education involves the application of a non-physical classroom, immersed in a creative and constant flux of complexity and trans-disciplinary processes; this is the social classroom born of the Trans-complex Educational Theory in response to the pandemic and post- pandemic phase of COVID-19. This case study will focus on the challenges to institutions, teachers and students, and relates to the struggle with acquiring new and complex skills. These struggles can be addressed using ‘R3 Education’ which promotes ‘Reinvention’, ‘Realignment’ and ‘Resilience’. The emergence of a responsive approach to curriculum design is now here - the trans-complex curriculum.

Mfn2 requires Hinge 1 integrity for efficient nucleotide-dependent assembly and membrane fusion

ABSTRACTMitofusins are members of the dynamin-related protein family, large GTPases that harness the energy from nucleotide hydrolysis to remodel membranes. Mitofusins possess four structural domains including two extended helical bundles that are connected by a flexible linker. The role of this linker (Hinge 1) in mitofusin-mediated membrane fusion is not well understood. We have characterized four variants with amino acid substitutions within this region of Mfn2. While a defect was not apparent in cells, a fusion deficiency was observed in vitro, and was rescued by the addition of cytosolic fraction. All four variants had decreased nucleotide-dependent assembly, which was improved by the addition of Bax. Assembly of mitofusins across two membranes was unaffected as formation of the trans complex was similar to wild type for all variants. We further demonstrate that variants with substitutions in both helical bundles are more severely impaired than any single mutant, suggesting that both helical bundles contribute to this function. Our data are consistent with a model where this region contributes to conformational changes that are important for assembly.

Chalcogen bonding of two ligands to hypervalent YF4 (Y = S, Se, Te, Po)

YF4 can engage in two simultaneous chalcogen bonds with a pair of bases. In cis dimer ligands are bound through σ-holes while in trans complex one ligand is held by σ-hole and another one by π-hole.

Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo

Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here, we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, Vps33/HOPS promotes productive SNARE assembly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially zipped, Sec17 promotes fusion in either the presence or absence of HOPS, but with faster kinetics when HOPS is absent, suggesting that ejection of the SM is a rate-limiting step.

Crystal and molecular structure of diorganoammonium oxalatotrimethylstannate, [R2NH2][Me3Sn(C2O4)] (R=i-Bu, cyclohexyl)

The title compounds [R2NH2][C2O4SnMe3](R=i-Bu, Cy), in which tin atoms adopt a distorted trigonal bipyramidal configuration, have been prepared and submitted to an X-ray diffraction study. These compounds have been obtained from the reaction of (Cy2NH2)2C2O4·H2O or (i-Bu2NH2)2C2O4 with SnMe3Cl. In both [R2NH2][C2O4SnMe3] compounds, the trans complex has an almost regular trigonal bipyramidal geometry around the tin atom. The SnMe3 residues are connected as a chain with bridging oxalate anions in a trans-SnC3O2 framework, the oxygen atoms being in axial positions. The cations connect linear adjacent chains through NH…O hydrogen bonds giving layered structures.

Capture and release of partially zipped trans-SNARE complexes on intact organelles

Soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptors (SNAREs) are hypothesized to trigger membrane fusion by complexing in trans through their membrane-distal N termini and zippering toward their membrane-embedded C termini, which in turn drives the two membranes together. In this study, we use a set of truncated SNAREs to trap kinetically stable, partially zipped trans-SNARE complexes on intact organelles in the absence of hemifusion and content mixing. We show that the C-terminal zippering of SNARE cytoplasmic domains controls the onset of lipid mixing but not the subsequent transition from hemifusion to full fusion. Moreover, we find that a partially zipped nonfusogenic trans-complex is rescued by Sec17, a universal SNARE cochaperone. Rescue occurs independently of the Sec17-binding partner Sec18, and it exhibits steep cooperativity, indicating that Sec17 engages multiple stalled trans-complexes to drive fusion. These experiments delineate distinct functions within the trans-complex, provide a straightforward method to trap and study prefusion complexes on native membranes, and reveal that Sec17 can rescue a stalled, partially zipped trans-complex.

Fixation of Copper(II) Ions in Aqueous Solution to Lignin Model Compound Vanillin in an Absence of the Nitrogen Donor Ligands; Structural and EPR Correlation

In order to elucidate the interactions of copper with wood, three mononuclear copper( II) coordination compounds with a vanillinate anion, cis-[Cu(C8H7O3)2(H2O)2] (1), trans- [Cu(C8H7O3)2(H2O)2]·2H2O (2), and trans-[Cu(C8H7O3)2(H2O)2] (3), have been characterized. X-ray structure analysis of the cis isomer 1 reveals two bidentate vanillinate ions coordinated via methoxy (Cu−O1 2.260(2) Å ) and deprotonated hydroxy oxygen atoms (Cu−O2 1.909(2) Å ), and two water molecules (Cu−O1w 2.087(2) Å ) in the octahedral CuO6 chromophore. Two axes O1−Cu−O1w’ in the octahedron have the same length, while the third axis O2−Cu−O2’ is shorter. This is in agreement with the room temperature EPR spectrum of 1, showing two signals (g12 2.302, g3 2.005), but interestingly, three signals (g1 2.393, g2 2.214, g3 2.010) in the 115 K spectrum were found. The same coordination atoms were found also in the trans isomer 2 (Cu−O2 1.950(2), Cu−O1w 1.994(2), Cu−O1 2.334(2) Å ), however here, two axes of almost equal length are short (O2−Cu−O2’ O1w−Cu−O1w’), while the third axis is longer (O1−Cu−O1’). On the other hand, three (rhombic) signals (g1 2.289, g2 2.163, g3 2.086) in the room temperature EPR spectrum of 2 suggest three different axes in the coordination octahedron. In the EPR spectrum, of the second trans complex 3, a slightly rhombically distorted elongated axial spectrum is found. The 115 K EPR spectra of the two trans complexes 2 and 3 do not differ significantly from the features observed at room temperature. These results indicate that there is not always a straightforward correlation between the results of XRD structure analysis and EPR spectroscopy. Nevertheless, both methods can act also complementarily and give a deeper insight into the nature of copper(II) chromophores.

[1H,15N] N.M.R. Kinetic Studies of Reactions of cis- and trans-[PtCl2(15NH3)(c-C6H1115NH2)] with Guanosine 5'-Monophosphate

cis-[PtCl2(15NH3)(c-C6H11NH2)] is an active metabolite of the oral platinum(IV) anticancer drug cis,trans,cis-[PtCl2(CH3CO2)2(NH2)(c-C6H11NH2)]. Since it is likely that guanine bases on DNA are targets for this drug, we have analysed the kinetics of reaction of this platinum(II) metabolite with guanosine 5′-monophosphate (5′-GMP) at 310 K, pH 7, using [1H, 15N] n.m.r. methods. Reactions of the trans isomer are reported for comparison. The reactions proceed via aquated intermediates, and, for the cis isomer, the rates of aquation and substitution of H2O by 5′-GMP are 2-5 times faster trans to the amine ligand (c-C6H11NH2) compared to trans to NH3 for both the first and second steps. For the trans complex, the first aquation step is c. 3 times faster than for the cis complex, as expected from the higher trans influence of Cl¯, whereas the rate of the second aquation step (trans to N7 of 5′-GMP) is comparable to that trans to NH3. These findings have implications for the courses of reactions with DNA.