On beyond “Detect and Respond” and “Secure by Design”

Sophos X-Ops unveils five-year investigation tracking China-based groups targeting perimeter devices

The Internet is full of cats—and in this case, malware-delivering fake cat websites used for very targeted search engine optimization.

Last month, Sophos X-Ops reported several MDR cases where threat actors exploited a vulnerability in Veeam backup servers. We continue to track the activities of this threat cluster, which recently included deployment of a new ransomware. The vulnerability, CVE-2024-40711, was used as part of a threat activity cluster we named STAC 5881. Attacks leveraged compromised […]

Jessica Y. Franco
Dec 1, 2020; 19:1936-1951
Research

Wenhe Zhu
Dec 29, 2020; 0:RA120.002353v1-mcp.RA120.002353
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Tricia Rowlison
Dec 1, 2020; 19:2090-2103
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Toma Keser
Dec 29, 2020; 0:RA120.002433v1-mcp.RA120.002433
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Yadong Yu
Dec 1, 2020; 19:1997-2014
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Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
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Kyle Swovick
Dec 28, 2020; 0:RA120.002301v1-mcp.RA120.002301
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Yi-Han Lin
Dec 1, 2020; 19:2030-2046
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Alba Simats
Dec 1, 2020; 19:1921-1935
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Ji Eun Kim
Dec 20, 2020; 0:RA120.002159v1-mcp.RA120.002159
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Eugen Netz
Dec 1, 2020; 19:2157-2167
Technological Innovation and Resources

Alison M. Kurimchak
Dec 1, 2020; 19:2068-2089
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Yi Liu
Dec 1, 2020; 19:1968-1985
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Zilu Ye
Dec 28, 2020; 0:R120.002204v1-mcp.R120.002204
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Charlotte A. G. H. van Gelder
Dec 1, 2020; 19:1952-1967
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Peter Lasch
Dec 1, 2020; 19:2125-2138
Technological Innovation and Resources

Sylwia Struk
Dec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766
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Weixian Deng
Dec 22, 2020; 0:RA120.002411v1-mcp.RA120.002411
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Julia Knöckel
Dec 22, 2020; 0:RA120.002432v1-mcp.RA120.002432
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Nadine Prust
Dec 17, 2020; 0:RA120.002232v1-mcp.RA120.002232
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R. Greg Stacey
Nov 4, 2020; 0:RA120.002275v1-mcp.RA120.002275
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Madison T Wright
Nov 18, 2020; 0:RA120.002168v1-mcp.RA120.002168
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David Durán
Nov 19, 2020; 0:RA120.002276v1-mcp.RA120.002276
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Sean A Burnap
Dec 7, 2020; 0:RA120.002305v1-mcp.RA120.002305
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Xinting Zhang
Dec 8, 2020; 0:RA120.002306v1-mcp.RA120.002306
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Mingkun Yang
Nov 24, 2020; 0:RA120.002144v1-mcp.RA120.002144
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Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
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Ka-Won Kang
Nov 30, 2020; 0:RA120.002169v1-mcp.RA120.002169
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Ryan J Lumpkin
Dec 2, 2020; 0:RA120.002414v1-mcp.RA120.002414
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Colin T. McDowell
Nov 24, 2020; 0:RA120.002256v1-mcp.RA120.002256
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Matthias Schittmayer
Dec 1, 2020; 19:2104-2114
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Laura F Fielden
Nov 11, 2020; 0:RA120.002370v1-mcp.RA120.002370
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Annika Nelde
Dec 7, 2020; 0:R120.002309v1-mcp.R120.002309
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Alison B. Ross
Nov 30, 2020; 0:R120.002190v1-mcp.R120.002190
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Congcong Lu
Nov 17, 2020; 0:R120.002257v1-mcp.R120.002257
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Tirsa L. E. van Westering
Dec 1, 2020; 19:2047-2067
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Jianhua Wang
Nov 4, 2020; 0:RA120.002375v1-mcp.RA120.002375
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Diana Samodova
Dec 1, 2020; 19:2139-2156
Technological Innovation and Resources

Philipp Emanuel Geyer
Dec 17, 2020; 0:RA120.002359v1-mcp.RA120.002359
Research

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.

The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor and lymphoid enhancer factor (TCF/LEF) serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor-suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.