The dark side of radiotherapy-induced cell death in cancer

The work of Dr. Sainz is supported by a Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain, a Coordinated grant from the Fundación Asociación Española Contra el Cáncer (AECC), and a Fondo de Investigaciones Sanitarias (FIS) grant PI15/ 01507 (co-financed through Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”) from the Instituto de Salud Carlos III (ISCIII), Spai

Runaway electrification of friable self-replicating granular matter

We establish that the nonlinear dynamics of collisions between particles favors the charging of a insulating, friable, self-replicating granular material that undergoes nucleation, growth, and fission processes; we demonstrate with a minimal dynamical model that secondary nucleation produces a positive feedback in an electrification mechanism that leads to runaway charging. We discuss ice as an example of such a self-replicating granular material: We confirm with laboratory experiments in which we grow ice from the vapor phase in situ within an environmental scanning electron microscope that charging causes fast-growing and easily breakable palm-like structures to form, which when broken off may form secondary nuclei. We propose that thunderstorms, both terrestrial and on other planets, and lightning in the solar nebula are instances of such runaway charging arising from this nonlinear dynamics in self-replicating granular matter

Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection in the United States and Europe. Despite the significant morbidity associated with prenatal HCMV infection, little is known about how the virus infects the fetus during pregnancy. To date, primary human cytotrophoblasts (CTBs) have been utilized to study placental HCMV infection and replication; however, the minimal mitotic potential of these cells restricts experimentation to a few days, which may be problematic for mechanistic studies of the slow-replicating virus. The aim of this study was to determine whether the human first trimester CTB cell line SGHPL-4 was permissive for HCMV infection and therefore could overcome such limitations. HCMV immediate early (IE) protein expression was detected as early as 3 hours post-infection in SGHPL-4 cells and progressively increased as a function of time. HCMV growth assays revealed the presence of infectious virus in both cell lysates and culture supernatants, indicating that viral replication and the release of progeny virus occurred. Compared to human fibroblasts, viral replication was delayed in CTBs, consistent with previous studies reporting delayed viral kinetics in HCMV-infected primary CTBs. These results indicate that SGHPL-4 cells are fully permissive for the complete HCMV replicative cycle. Our findings suggest that these cells may serve as useful tools for future mechanistic studies of HCMV pathogenesis during early pregnancy

Cancer stem cells and macrophages: Implications in tumor biology and therapeutic strategies

This work was supported by a Ramón y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain (Bruno Sainz Jr.), a Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY (Bruno Sainz Jr.), and an NIH/NCI R00 (CA154605, Heather L. Machad

Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with the innate IFNs (IFN-α and IFN-β) to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV) replication. RESULTS: We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β) to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs) with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE) genes (IE1 and IE2) revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold) as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. CONCLUSION: These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo

The cancer stem cell in hepatocellular carcinoma

The recognition of intra-tumoral cellular heterogeneity has given way to the concept of the cancer stem cell (CSC). According to this concept, CSCs are able to self-renew and differentiate into all of the cancer cell lineages present within the tumor, placing the CSC at the top of a hierarchical tree. The observation that these cells—in contrast to bulk tumor cells—are able to exclusively initiate new tumors, initiate metastatic spread and resist chemotherapy implies that CSCs are solely responsible for tumor recurrence and should be therapeutically targeted. Toward this end, dissecting and understanding the biology of CSCs should translate into new clinical therapeutic approaches. In this article, we review the CSC concept in cancer, with a special focus on hepatocellular carcinoma.Work in the laboratory of P.C.H. is supported by a Max Eder Fellowship of the German Cancer Aid (111746), by a Collaborative Research Centre grant of the German Research Foundation (316249678–SFB 1279) and by a Hector Foundation Cancer Research grant (M65.1). Work in the laboratory of B.S.J. is supported by a Rámon y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economía y Competitividad, Spain. L.-A.S. is supported by the clinician scientist program of Ulm Universit

Hacking computers by USB ports

Trabajo de Fin de Grado en Ingeniería del Software, Facultad de Informática UCM, Departamento de Arquitectura de Computadores y Automática, Curso 2021/2022.Los ataques HID (Human Interface Device) consisten en conectar un pequeño sistema empotrado al puerto USB del computador víctima para que este lo identifique como un dispositivo USB válido y poder explotar sus vulnerabilidades por este medio. Ciñéndose a Raspberry Pi Zero W como sistema empotrado atacante, los objetivos de este trabajo consisten en estudiar el funcionamiento del puerto USB, así como la vulnerabilidad que posee y que hace posible que se pueda atacar con facilidad, las herramientas existentes para estos ataques (como P4wnP1 A.L.O.A, Ethsploiter, entre otros), ponerlas a prueba en diversos sistemas, para posteriormente ofrecer soluciones para evitar que puedan llegar a ejecutarse estas herramientas. Para cada herramienta utilizada haremos un tutorial de instalación, una explicación de su funcionamiento, una pequeña demostración en diferentes entornos y una posible solución para hacer frente a las vulnerabilidades explotadas. Además, explicaremos los diferentes tipos de ataques HID, como montar cualquier imagen en una Raspberry Pi Zero, la definición de exploit y en qué se diferencia con una vulneravilidad y los distintos tipos de estos. Complementandolo con nuestra conclusión respecto a estos tipos de ataques muy presentes en el mundo real debido a su facilidad en realizarlos y a su dificultad en defenderse de ellos.Depto. de Arquitectura de Computadores y AutomáticaFac. de InformáticaTRUEunpu

Competing structures in a minimal double-well potential model of condensed matter

The microscopic structure of several amorphous substances often reveals complex patterns such as medium- or long-range order, spatial heterogeneity, and even local polycrystallinity. To capture all these features, models usually incorporate a refined description of the particle interaction which includes an ad hoc design of the inside of the system constituents. We show that all these features can emerge from a minimal two-dimensional model where particles interact isotropically by a double-well potential, and have an excluded volume and a maximum coordination number. The rich variety of structural patterns shown by this simple model apply to a wide catalogue of real systems including water, silicon, and different amorphous materials.Comment: 5 pages, 5 figure

Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment

The first steps towards establishing xenografts in zebrafish embryos were performed by Lee et al., 2005 and Haldi et al., 2006, paving the way for studying human cancers using this animal species. Since then, the xenograft technique has been improved in different ways, ranging from optimizing the best temperature for xenografted embryo incubation, testing different sites for injection of human tumor cells, and even developing tools to study how the host interacts with the injected cells. Nonetheless, a standard protocol for performing xenografts has not been adopted across laboratories, and further research on the temperature, microenvironment of the tumor or the cell–host interactions inside of the embryo during xenografting is still needed. As a consequence, current non-uniform conditions could be affecting experimental results in terms of cell proliferation, invasion, or metastasis; or even overestimating the effects of some chemotherapeutic drugs on xenografted cells. In this review, we highlight and raise awareness regarding the different aspects of xenografting that need to be improved in order to mimic, in a more efficient way, the human tumor microenvironment, resulting in more robust and accurate in vivo resultsConsellería de Educación, Universidade e Formación Profesional (ED431C 2018/28)S