Optimizing the parameters for hydro-jet dissection in fatty tissue — A morphological Ex Vivo analysis

Summary: Background: The advantage of water-jet dissection is the preservation of vessels and nerves. Especially in liver surgery, blood loss can be significantly decreased. The use of water-jet dissectors in other fields of surgery is currently under investigation. The preparation of vessels in fatty tissue is of special interest for plastic surgeons. The optimal technical parameters were investigated. Methods: Abdominal fat tissue of fresh cadavers was cut under standardized conditions with different parameters of the water-jet dissector. Results: One single pass at a cutting pressure between 20 and 60 Bar makes an incision of 8 mm. Deeper cuts can be achieved by repeated application on the same cut. Five passes at 40 Bar results in a depth of 1.7 cm without vessel damage. If the applied pressure is 50 or 60 Bar, up to 7% damaged vessels can be found. The water-jet dissection leads to a water uptake of the cut tissue. Conclusions: The optimal pressure for water-jet dissection of fatty tissue lies between 30 and 40 Bar. The effect of the mechanical irritation of the vessels has to be investigatedin vivo before using the water-jet dissector for preparation of blood vessels in humans, e.g. for flap dissectio

The long non-coding {RNA} {H19} suppresses carcinogenesis and chemoresistance in hepatocellular carcinoma

The long non-coding RNA (lncRNA) H19 represents a maternally expressed and epigenetically regulated imprinted gene product and is discussed to have either tumor-promoting or tumor-suppressive actions. Recently, H19 was shown to be regulated under inflammatory conditions. Therefore, aim of this study was to determine the function of H19 in hepatocellular carcinoma (HCC), an inflammation-associated type of tumor. In four different human HCC patient cohorts H19 was distinctly downregulated in tumor tissue compared to normal or non-tumorous adjacent tissue. We therefore determined the action of H19 in three different human hepatoma cell lines (HepG2, Plc/Prf5, and Huh7). Clonogenicity and proliferation assays showed that H19 overexpression could suppress tumor cell survival and proliferation after treatment with either sorafenib or doxorubicin, suggesting chemosensitizing actions of H19. Since HCC displays a highly chemoresistant tumor entity, cell lines resistant to doxorubicin or sorafenib were established. In all six chemoresistant cell lines H19 expression was significantly downregulated. The promoter methylation of the H19 gene was significantly different in chemoresistant cell lines compared to their sensitive counterparts. Chemoresistant cells were sensitized after H19 overexpression by either increasing the cytotoxic action of doxorubicin or decreasing cell proliferation upon sorafenib treatment. An H19 knockout mouse model (H19Δ3) showed increased tumor development and tumor cell proliferation after treatment with the carcinogen diethylnitrosamine (DEN) independent of the reciprocally imprinted insulin-like growth factor 2 (IGF2). In conclusion, H19 suppresses hepatocarcinogenesis, hepatoma cell growth, and HCC chemoresistance. Thus, mimicking H19 action might be a potential target to overcome chemoresistance in future HCC therapy

Cellular Ca2+ signals generate defined pH signatures in plants

Calcium ions (Ca2+) play a key role in cell signaling across organisms. The question of how a simple ion can mediate specificity has spurred research into the role of Ca2+ signatures and their encoding and decoding machinery. Such studies have frequently focussed on Ca2+ alone and our understanding of how Ca2+ signalling is integrated with other responses remains poorly understood. Using in vivo imaging with different genetically-encoded fluorescent sensors in Arabidopsis cells we show that Ca2+ transients do not occur in isolation but are accompanied by pH changes in the cytosol. We estimate the degree of cytosolic acidification at up to 0.25 pH units in response to external ATP in seedling root tips. We validated this pH-Ca2+ link for distinct stimuli. Our data suggest that the association with pH may be a general feature of Ca2+ transients that depends on the transient characteristics and the intracellular compartment. These findings suggest a fundamental link between Ca2+ and pH dynamics in plant cells, generalizing previous observations of their association in growing pollen tubes and root hairs. Ca2+ signatures act in concert with pH signatures, possibly providing an additional layer of cellular signal transduction to tailor signal specificity

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

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

First passage and first hitting times of Lévy flights and Lévy walks

Abstract For both Lévy flight and Lévy walk search processes we analyse the full distribution of first-passage and first-hitting (or first-arrival) times. These are, respectively, the times when the particle moves across a point at some given distance from its initial position for the first time, or when it lands at a given point for the first time. For Lévy motions with their propensity for long relocation events and thus the possibility to jump across a given point in space without actually hitting it (‘leapovers’), these two definitions lead to significantly different results. We study the first-passage and first-hitting time distributions as functions of the Lévy stable index, highlighting the different behaviour for the cases when the first absolute moment of the jump length distribution is finite or infinite. In particular we examine the limits of short and long times. Our results will find their application in the mathematical modelling of random search processes as well as computer algorithms

Search reliability and search efficiency of combined Lévy–Brownian motion: long relocations mingled with thorough local exploration

A combined dynamics consisting of Brownian motion and Levy flights is exhibited by a variety of biological systems performing search processes. Assessing the search reliability of ever locating the target and the search efficiency of doing so economically of such dynamics thus poses an important problem. Here we model this dynamics by a one-dimensional fractional Fokker-Planck equation combining unbiased Brownian motion and Levy flights. By solving this equation both analytically and numerically we show that the superposition of recurrent Brownian motion and Levy flights with stable exponent α<1, by itself implying zero probability of hitting a point on a line, lead to transient motion with finite probability of hitting any point on the line. We present results for the exact dependence of the values of both the search reliability and the search efficiency on the distance between the starting and target positions as well as the choice of the scaling exponent α of the Levy flight component