פרסומים

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy. The TrC was proved in human prostate cancer cells with different malignancy potential, and in human bladder cancer and melanoma cells that were sorted into subpopulations based solely on their phagocytic capacity. The more phagocytic subpopulations showed elevated aggressiveness ex vivo and in vivo. The uptake potential was preserved, and differences in gene expression and in epigenetic signature were detected. In all cases, enhanced phagocytic and aggressiveness phenotypes were correlated with greater cell deformability and predicted by a computational model. Our multidisciplinary study provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy. The TrC was proved in human prostate cancer cells with different malignancy potential, and in human bladder cancer and melanoma cells that were sorted into subpopulations based solely on their phagocytic capacity. The more phagocytic subpopulations showed elevated aggressiveness ex vivo and in vivo. The uptake potential was preserved, and differences in gene expression and in epigenetic signature were detected. In all cases, enhanced phagocytic and aggressiveness phenotypes were correlated with greater cell deformability and predicted by a computational model. Our multidisciplinary study provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy. The TrC was proved in human prostate cancer cells with different malignancy potential, and in human bladder cancer and melanoma cells that were sorted into subpopulations based solely on their phagocytic capacity. The more phagocytic subpopulations showed elevated aggressiveness ex vivo and in vivo. The uptake potential was preserved, and differences in gene expression and in epigenetic signature were detected. In all cases, enhanced phagocytic and aggressiveness phenotypes were correlated with greater cell deformability and predicted by a computational model. Our multidisciplinary study provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.

Embryonic stem cells (ESC) have the ability to epigenetically silence endogenous and exogenous retroviral sequences. Trim28 plays an important role in establishing this silencing, but less is known about the role other Trim proteins play. The Tif1 family is a sub-group of the Trim family, which possess histone binding ability in addition to the distinctive RING domain. Here, we have examined the interaction between three Tif1 family members, namely Trim24, Trim28 and Trim33, and their function in retroviral silencing. We identify a complex formed in ESC, comprised of these three proteins. We further show that when Trim33 is depleted, the complex collapses and silencing efficiency of both endogenous and exogenous sequences is reduced. Similar transcriptional activation takes place when Trim24 is depleted. Analysis of the H3K9me3 chromatin modification showed a decrease in this repressive mark, following both Trim24 and Trim33 depletion. As Trim28 is an identified binding partner of the H3K9 methyltransferase ESET, this further supports the involvement of Trim28 in the complex. The results presented here suggest that a complex of Tif1 family members, each of which possesses different specificity and efficiency, contributes to the silencing of retroviral sequences in ESC.

The essence of turbulent flow is the conveyance of energy through the formation, interaction, and destruction of eddies over a wide range of spatial scales-from the largest scales where energy is injected down to the smallest scales where it is dissipated through viscosity. Currently, there is no mechanistic framework that captures how the interactions of vortices drive this cascade. We show that iterations of the elliptical instability, arising from the interactions between counter-rotating vortices, lead to the emergence of turbulence. We demonstrate how the nonlinear development of the elliptical instability generates an ordered array of antiparallel secondary filaments. The secondary filaments mutually interact, leading to the formation of even smaller tertiary filaments. In experiments and simulations, we observe two and three iterations of this cascade, respectively. Our observations indicate that the elliptical instability could be one of the fundamental mechanisms by which the turbulent cascade develops.

Data collection from online platforms, such as Mechanical Turk (MTurk), has become popular in clinical research. However, there are also concerns about the representativeness and the quality of this data for clinical studies. The present work explores these issues in the specific case of major depression. Analyses of two large data sets gathered from MTurk (N1 = 2,692 and N2 = 2,354) revealed two major findings: First, failing to screen for inattentive and fake respondents inflates the rates of major depression artificially and significantly (to 18.5% to 27.5%). Second, after cleaning the data sets, depression in MTurk is still 1.6 to 3.6 times higher than general population estimates. Approximately half of this difference can be attributed to differences in the composition of MTurk samples and the general population (i.e., socio-demographics, health and physical activity lifestyle). Several explanations for the other half are proposed and practical data-quality tools are provided. 

Channelrhodopsins (ChR) are light-gated ion-channels heavily used in optogenetics. Upon light excitation an ultrafast all-trans to 13-cis isomerization of the retinal chromophore takes place. It is still uncertain by what means this reaction leads to further protein changes and channel conductivity. Channelrhodopsin-1 in Chlamydomonas augustae exhibits a 100 fs photoisomerization and a protonated counterion complex. By polarization resolved ultrafast spectroscopy in the mid-IR we show that the initial reaction of the retinal is accompanied by changes in the protein backbone and ultrafast protonation changes at the counterion complex comprising Asp299 and Glu169. In combination with homology modelling and quantum mechanics/molecular mechanics (QM/MM) geometry optimization we assign the protonation dynamics to ultrafast deprotonation of Glu169, and transient protonation of the Glu169 backbone, followed by a proton transfer from the backbone to the carboxylate group of Asp299 on a timescale of tens of picoseconds. The second proton transfer is not related to retinal dynamics and reflects pure protein changes in the first photoproduct. We assume these protein dynamics to be the first steps in a cascade of protein-wide changes resulting in channel conductivity. 

{As one of the most important physical processes of strong-field laser-matter interaction, laser-driven electron-ion recollision is the fundamental process. As we have known, the well-known three-step model of HHG predicts that the cutoff law obeys Ecutoffþinspace=þinspace

Abstract Gaining an understanding of the conformational behavior of fluorinated compounds would allow for expansion of the current molecular design toolbox. In order to facilitate drug discovery efforts, a systematic survey of a series of diversely substituted and protected fluorinated piperidine derivatives has been carried out using NMR spectroscopy. Computational investigations reveal that, in addition to established delocalization forces such as charge?dipole interactions and hyperconjugation, solvation and solvent polarity play a major role. This work codifies a new design principle for conformationally rigid molecular scaffolds.

The metastatistical extreme value approach proved promising in the frequency analysis of daily precipitation from ordinary events, outperforming traditional methods based on sampled extremes. However, subdaily applications are currently restrained by two knowledge gaps: It is not known if ordinary events can be consistently examined over durations, and it is not clear to what extent their entire distributions represent extremes. We propose here a unified definition of ordinary events across durations and suggest the simplified metastatistical extreme value formulation for dealing with extremes emerging from the tail, rather than the entire distributions, of ordinary events. This unified framework provides robust estimates of extreme quantiles (\textless10% error on the 100 yr from a 26 yr long record) and allows representations in which ordinary and extreme events share the scaling exponent. Future applications could improve our knowledge of subdaily extreme precipitation and help investigate the impact of local factors and climatic forcing on their frequency.

The need to ensure that people have adequate savings for retirement has prompted debate among regulators and academics. Certain countries have implemented or are considering implementing mandatory minimum annuity laws (e.g., Singapore and Israel), whereas others have repealed or are considering repealing such legislation (e.g., the U.K.). We investigate the introduction as well as the repeal of a regulatory change—specifically, a mandatory minimum annuity rule—using a laboratory experiment and two surveys. Our results indicate that imposing a mandatory minimum may create an anchoring effect to the threshold level. Furthermore, our results suggest that the mandatory requirement may have unintended consequences: Such laws may fail to provide an increase in the demand for annuities and may even reduce it for certain individuals. The outcome is sensitive to the relation between the level of the mandatory minimum and anticipated consumption (i.e., future financial need). Moreover, we provide novel evidence about the consequences of a repeal of mandatory minimum annuity laws and suggest that it may not restore the demand for annuities to the pre-law level.