Proton gradients and pH oscillations emerge from heat flow at the microscale

Proton gradients are essential for biological systems. They not only drive the synthesis of ATP, but initiate molecule degradation and recycling inside lysosomes. However, the high mobility and permeability of protons through membranes make pH gradients very hard to sustain in vitro. Here we report that heat flow across a water-filled chamber forms and sustains stable pH gradients. Charged molecules accumulate by convection and thermo- phoresis better than uncharged species. In a dissociation reaction, this imbalances the reaction equilibrium and creates a difference in pH. In solutions of amino acids, phosphate, or nucleotides, we achieve pH differences of up to 2 pH units. The same mechanism cycles biomolecules by convection in the created proton gradient. This implements a feedback between biomolecules and a cyclic variation of the pH. The finding provides a mechanism to create a self-sustained proton gradient to drive biochemical reactions

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

A DNA-Based Biosensor Assay for the Kinetic Characterization of Ion-Dependent Aptamer Folding and Protein Binding

Therapeutic and diagnostic nucleic acid aptamers are designed to bind tightly and specifically to their target. The combination of structural and kinetic analyses of aptamer interactions has gained increasing importance. Here, we present a fluorescence-based switchSENSE aptasensor for the detailed kinetic characterization of aptamer–analyte interaction and aptamer folding, employing the thrombin-binding aptamer (TBA) as a model system. Thrombin-binding aptamer folding into a G-quadruplex and its binding to thrombin strongly depend on the type and concentration of ions present in solution. We observed conformational changes induced by cations in real-time and determined the folding and unfolding kinetics of the aptamer. The aptamer’s affinity for K+ was found to be more than one order of magnitude higher than for other cations (K+ > NH4+ >> Na+ > Li+). The aptamer’s affinity to its protein target thrombin in the presence of different cations followed the same trend but differed by more than three orders of magnitude (KD = 0.15 nM to 250 nM). While the stability (kOFF) of the thrombin–TBA complex was similar in all conditions, the cation type strongly influenced the association rate (kON). These results demonstrated that protein–aptamer binding is intrinsically related to the correct aptamer fold and, hence, to the presence of stabilizing ions. Because fast binding kinetics with on-rates exceeding 108 M−1s−1 can be quantified, and folding-related phenomena can be directly resolved, switchSENSE is a useful analytical tool for in-depth characterization of aptamer–ion and aptamer–protein interactions

A Double-Edged Sword? On the Benefit, Detriment, and Net Effect of Dimensional Comparison on Self-Concept

Dimensional comparison theory (DCT; Möller & Marsh, 2013) assumes that students compare their academic achievement intraindividually across domains to form domain-specific self-concepts. Upward dimensional comparisons are believed to lead to lower self-concepts in the worse-off domain, while downward dimensional comparisons should lead to higher self-concepts in the better-off domain. Furthermore, DCT assumes the net effect of upward and downward dimensional comparisons to be beneficial to the self. To test these assumptions, 3 experiments and 2 field studies were conducted investigating the relative effects of upward and downward dimensional comparisons as well as their net effect. In Studies 1 (N = 149), 2 (N = 150) and 3 (N = 300), participants were asked to infer self-concepts of fictitious students after receiving experimentally manipulated information about their achievements in 2 domains, whereas participants in Studies 4 (N = 2,268) and 5 (N = 20,662) assessed their own self-concepts in German and mathematics. In all studies, downward dimensional comparisons resulted in higher self-concepts, whereas upward dimensional comparisons led to lower self-concepts. The net effect of dimensional comparisons was always found to be not statistically different from zero. The findings therefore support the central prediction of DCT on the discreteness of the effects of upward and downward dimensional comparisons, yet do not support the assumed positivity of their net effect. Furthermore, results indicate the effect patterns to be rather universal as they were stable across different samples, domains, achievement situations, research designs, and types of assessment

Synthesis and Application of Low Molecular Weight PEI-based Copolymers for siRNA Delivery with Smart Polymer Blends.

Polyethylenimine (PEI) is a commonly used cationic polymer for small-interfering RNA (siRNA) delivery due to its high transfection efficiency at low commercial cost. However, high molecular weight PEI is cytotoxic and thus, its practical application is limited. In this study, we investigated different formulations of low molecular weight PEI (LMW-PEI) based copolymers PEI-PCL (800 Da-40 kDa) and PEI-PCL-PEI (5 kDa-5 kDa-5 kDa) blended with or without PEG-PCL (5 kDa-4 kDa) to prepare nanoparticles via nanoprecipitation using a solvent displacement method with sizes around 100 nm. PEG-PCL can stabilize the nanoparticles, improve their biocompatibility, and extend their circulation time in vivo. The nanoparticles composed of PEI-PCL-PEI and PEG-PCL showed higher siRNA encapsulation efficiency than PEI-PCL/PEG-PCL based nanoparticles at low N/P ratios, higher cellular uptake, and a gene silencing efficiency of around 40% as a result of the higher molecular weight PEI blocks. These results suggested that the PEI-PCL-PEI/PEG-PCL nanoparticle system could be a promising vehicle for siRNA delivery at minimal synthetic effort. This article is protected by copyright. All rights reserved

Dimensional comparison theory: New models, new methods, new insights

Möller J, Wolff F, Helm F. Dimensional comparison theory: New models, new methods, new insights. In: Dicke T, Marsh HW, Craven RG, McInerney DM, eds. Self: A multidisciplinary concept. Information Age Publishing; 2021: 31-57

Testing the dimensional comparison theory: When do students prefer dimensional comparisons to social and temporal comparisons?

Wolff F, Helm F, Möller J. Testing the dimensional comparison theory: When do students prefer dimensional comparisons to social and temporal comparisons? Social Psychology of Education. 2018;21(4):875-895

The Marine Biodiversity Observation Network Plankton Workshops: Plankton Ecosystem Function, Biodiversity, and Forecasting—Research Requirements and Applications

ISSN:1539-6088ISSN:1539-607