Fragility and compressibility at the glass transition

Isothermal compressibilities and Brillouin sound velocities from the literature allow to separate the compressibility at the glass transition into a high-frequency vibrational and a low-frequency relaxational part. Their ratio shows the linear fragility relation discovered by x-ray Brillouin scattering [1], though the data bend away from the line at higher fragilities. Using the concept of constrained degrees of freedom, one can show that the vibrational part follows the fragility-independent Lindemann criterion; the fragility dependence seems to stem from the relaxational part. The physical meaning of this finding is discussed. [1] T. Scopigno, G. Ruocco, F. Sette and G. Monaco, Science 302, 849 (2003)Comment: 4 pages, 2 figures, 2 tables, 33 references. Slightly changed after refereein

GeneSigDB—a curated database of gene expression signatures

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats

+1,5° C: Wieviel Treibhausgase dürfen wir noch emittieren? CCCA Fact Sheet #40

Um die globale Erwärmung und somit die Auswirkungen des Klimawandels, wie im Pariser Übereinkommen festgelegt, auf +1,5 °C bzw. unter +2 °C gegenüber dem vorindustriellen Niveau (1850-1900) zu begrenzen muss für die Klimaneutralitätsziele die Gesamtmenge an Treibhausgas (THG)-Emissionen entsprechend beschränkt werden. Unter aktuellen Maßnahmenplänen, ohne zusätzliche Schritte, bewegen wir uns noch in diesem Jahrhundert auf +2,8 °C zu, was deutlich größere Schäden und Verluste zur Folge hätte. Das Factsheet basiert auf der umfangreichen Ausarbeitung in: CCCA (2022): +1,5° C: Wieviel Treibhausgase dürfen wir noch emittieren? Hintergrundpapier zu globalen und nationalen Treibhausgasbudgets. K. Steininger, T. Schinko, H. Rieder, H. Kromp-Kolb, S. Kienberger, G. Kirchengast, C. Michl, I. Schwarzl, S. Lambert. Wien: CCC

Mechanical Relaxation in Glasses and at the Glass Transition

The Gilroy-Phillips model of relaxational jumps in asymmetric double-well potentials, developed for the Arrhenius-type secondary relaxations of the glass phase, is extended to a formal description of the breakdown of the shear modulus at the glass transition, the flow process.Comment: 13 pages, 11 figures, 49 ref

A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Aim Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. Methods Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipi‑ tation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. Results We identifed IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was signif‑ cantly associated with resistance to selumetinib, geftinib, and regorafenib in PDOs and to 5-fuorouracil and oxalipl‑ atin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabiliza‑ tion of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidifcation rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confrmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. Conclusions IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mito‑ chondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance

Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and HBs displayed differing solubility properties and distinct distribution patterns, HBs-PiZ animals manifested retention of AAT/HBs in the degradatory pathway and a marked accumulation of the autophagy adaptor p62. Isolation of p62-containing particles revealed retained HBs/AAT and the lipophagy adapter perilipin-2. p62 build-up led to activation of the p62–Nrf2 axis and emergence of reactive oxygen species. Our results demonstrate that the simultaneous presence of two prevalent proteotoxic stresses promotes the development of liver injury due to protein retention and activation of the p62–Nrf2 axis. In humans, the PiZ variant was over-represented in CHB patients with advanced liver fibrosis (unadjusted odds ratio = 9.92 [1.15–85.39]). Current siRNA approaches targeting HBs/AAT should be considered for these individuals. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

A constitutive representation for linear aging, environmental-dependent viscoelastic materials

This study is concerned with developing a constitutive law for aging and environmental-dependent materials. The development rests on the assumption that the mechanical properties of the aforementioned materials can be mathematically represented by a functional of the strain and environmental histories, and this functional depends on the present time and the time the material is created. This constitutive assumption leads to two equivalent integral forms of the constitutive law after asserting that the functional is linear in the strain history. The first form of the integral law contains a material response functional analogous to the creep and relaxation functions of classical linear viscoelasticity. The second integral law has the same basic mathematical form but the physical interpretation of the mechanical response functional is different. It is demonstrated that both forms of the aging law reduce to the same non-aging law which is the usual starting for an analysis of only environmental-dependent materials. In the Appendix an operator algebra is presented for convenience in manipulating the integral laws for aging materials. Diese Untersuchung beschäftigt sich mit der Darstellung eines Werkstoffgesetzes für Altern und für umgebungsabhängige Stoffe. Die Entwicklung beruht auf der Annahme, daß die mechanischen Eigenschaften der oben erwähnten Stoffe mathematisch durch ein Funktional der Verzerrungs- und der Umgebungsgeschichten dargestellt werden kann und daß dieses Funktional von der augenblicklichen Zeit und der Zeit der Erzeugung des Stoffes abhängt. Diese Werkstoffannahme führt, unter der Voraussetzung einer linearen Abhängigkeit des Funktionals von der Verzerrungsgeschichte, auf zwei äquivalente Integraldarstellungen des Werkstoffgesetzes. Die erste Darstellung des Integralgesetzes enthält ein Materialantwort-Funktional analog der Kriech- und Relaxationsfunktionen der klassischen linearen Viskoelastizität. Das zweite Gesetz hat die gleiche mathematische Gestalt, aber verschiedene physikalische Interpretation des mechanischen Antwort-Funktionals. Es wird gezeigt, daß für nicht-alternde Stoffe beide Darstellungen dasselbe Gesetz, das der übliche Ausgangspunkt einer Untersuchung umgebungsbeeinflußter Stoffe ist, ergeben. Im Anhang werden einige für das Rechnen mit den Integralgesetzen alternder Stoffe handliche Sätze der Operatorenrechnung angegeben.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41700/1/707_2005_Article_BF01179657.pd