Low Temperature Stabilization of Nanoscale Epitaxial Spinel Ferrite Thin Films by Atomic Layer Deposition

In this work heteroepitaxial stabilization with nanoscale control of the magnetic Co₂FeO₄ phase at 250 °C is reported. Ultrasmooth and pure Co₂FeO₄ thin films (5–25 nm) with no phase segregation are obtained on perovskite SrTiO₃ single crystal (100) and (110) oriented substrates by atomic layer deposition (ALD). High resolution structural and chemical analyses confirm the formation of the Co‐rich spinel metastable phase. The magneto‐crystalline anisotropy of the Co₂FeO₄ phase is not modified by stress anisotropy because the films are fully relaxed. Additionally, high coervice fields, 15 kOe, and high saturation of magnetization, 3.3 μ_B per formula unit (at 10 K), are preserved down to 10 nm. Therefore, the properties of the ALD‐Co₂FeO₄ films offer many possibilities for future applications in sensors, actuators, microelectronics, and spintronics. In addition, these results are promising for the use of ALD compared to the existing thin‐film deposition techniques to stabilize epitaxial multicomponent materials with nanoscale control on a wide variety of substrates for which the processing temperature is a major drawback.     

Annotating the argument structure of deverbal nominalizations in Spanish

Over recent years, there has been a growing interest in the computational treatment of nominalized Noun Phrases due to the rich semantic information they contain. These Noun Phrases can be understood as verbal paraphrases and, just like them, they can also denote argument and thematic-role relations. This paper presents the methodology followed to annotate the argument structure of deverbal nominalizations in the Spanish AnCora-Es corpus. We focus on the automated annotation process that is mostly based on the semantic information specified in a verbal lexicon but also on the syntactic and semantic information annotated in the corpus. The heuristic rules that make use of this information rely on linguistic assumptions that are also evaluated as we evaluate the reliability of the automated process. The automated annotation was manually checked in order to ensure the accuracy of the final resource. We demonstrate its feasibility (77% F-measure) and show that it facilitates corpus annotation, which is always a time-consuming and costly process. The result is the enrichment of the AnCora-Es corpus with the argument structure and thematic roles of deverbal nominalizations. It is the first Spanish corpus with this kind of information that is freely available.     

Is DNA Damage Response Ready for Action Anywhere?

Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.     

Anwendungspotenzial von Membranprozessen im Konzept der Lignocellulose-Bioraffinerien

The pulp and paper industry is one of the most important industrial sectors worldwide and has a great potential to be a cornerstone for the future bio-economy, in particular lignocellulosic bio-refineries. The potential of the membrane processes in this conversion will be highlighted in three applications related to kraft/sulphate, sulphite and thermomechanical pulping. Furthermore, the challenges of membrane fouling and cleaning with regard to pulping industry will be discussed and an outlook on future developments of membranes in biorefineries will be given.     

Fluorescent Markers for Amyloid-β Detection: Computational Insights

In vivo detection of cerebral amyloid-β plaques is essential for an early diagnosis of Alzheimer′s disease. Optical imaging, which employs fluorescent markers emitting in the near-infrared range, is a growing alternative to nuclear techniques, with indisputable advantages. The rational design of amyloid markers requires optimization of both the optical and binding properties, and of their mutual interaction. In this work, the structural aspects that determine the performance of selected amyloid markers have been analyzed, focusing on the contributions offered by computational techniques.     

Entrectinib—A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells

Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.     

AC-265347 Inhibits Neuroblastoma Tumor Growth by Induction of Differentiation without Causing Hypocalcemia

Neuroblastoma is the most common extracranial solid tumor of childhood, with heterogeneous clinical manifestations ranging from spontaneous regression to aggressive metastatic disease. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that senses plasmatic fluctuation in the extracellular concentration of calcium and plays a key role in maintaining calcium homeostasis. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. The activation of CaSR with cinacalcet, a positive allosteric modulator of CaSR, reduces neuroblastoma tumor growth by promoting differentiation, endoplasmic reticulum (ER) stress and apoptosis. However, cinacalcet treatment results in unmanageable hypocalcemia in patients. Based on the bias signaling shown by calcimimetics, we aimed to identify a new drug that might exert tumor-growth inhibition similar to cinacalcet, without affecting plasma calcium levels. We identified a structurally different calcimimetic, AC-265347, as a promising therapeutic agent for neuroblastoma, since it reduced tumor growth by induction of differentiation, without affecting plasma calcium levels. Microarray analysis suggested biased allosteric modulation of the CaSR signaling by AC-265347 and cinacalcet towards distinct intracellular pathways. No upregulation of genes involved in calcium signaling and ER stress were observed in patient-derived xenografts (PDX) models exposed to AC-265347. Moreover, the most significant upregulated biological pathways promoted by AC-265347 were linked to RHO GTPases signaling. AC-265347 upregulated cancer testis antigens (CTAs), providing new opportunities for CTA-based immunotherapies. Taken together, this study highlights the importance of the biased allosteric modulation when targeting GPCRs in cancer. More importantly, the capacity of AC-265347 to promote differentiation of malignant neuroblastoma cells provides new opportunities, alone or in combination with other drugs, to treat high-risk neuroblastoma patients.     

In Silico Study of Allosteric Communication Networks in GPCR Signaling Bias

Signaling bias is a promising characteristic of G protein-coupled receptors (GPCRs) as it provides the opportunity to develop more efficacious and safer drugs. This is because biased ligands can avoid the activation of pathways linked to side effects whilst still producing the desired therapeutic effect. In this respect, a deeper understanding of receptor dynamics and implicated allosteric communication networks in signaling bias can accelerate the research on novel biased drug candidates. In this review, we aim to provide an overview of computational methods and techniques for studying allosteric communication and signaling bias in GPCRs. This includes (i) the detection of allosteric communication networks and (ii) the application of network theory for extracting relevant information pipelines and highly communicated sites in GPCRs. We focus on the most recent research and highlight structural insights obtained based on the framework of allosteric communication networks and network theory for GPCR signaling bias.