HIPK2 in cancer biology and therapy: Recent findings and future perspectives

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates and regulates a plethora of transcriptional regulators and chromatin modifiers. The heterogeneity of its interactome allows HIPK2 to modulate several cellular processes and signaling pathways, ultimately regulating cell fate and proliferation. Because of its p53-dependent pro-apoptotic activity and its downregulation in many tumor types, HIPK2 is traditionally considered a bone fide tumor suppressor gene. However, recent findings revealed that the role of HIPK2 in the pathogenesis of cancer is much more complex, ranging from tumor suppressive to oncogenic, strongly depending on the cellular context. Here, we review the very recent data emerged in the last years about the involvement of HIPK2 in cancer biology and therapy, highlighting the various alterations of this kinase (downregulation, upregulation, mutations and/or delocalization) in dependence on the cancer types. In addition, we discuss the recent advancement in the understanding the tumor suppressive and oncogenic functions of HIPK2, its role in establishing the response to cancer therapies, and its regulation by cancer-associated microRNAs. All these data strengthen the idea that HIPK2 is a key player in many types of cancer; therefore, it could represent an important prognostic marker, a factor to predict therapy response, and even a therapeutic target itself

The use of virtual environments for survey spatial ability evaluation in topographical disorientation

Due to their interactivity and to the sense of presence they afford, virtual environments constitute an interesting opportunity to study spatial cognition. In accordance with this perspective, we aimed to introduce a spatial test in virtual simulation in order to investigate the survey spatial ability in patients with topographical disorientation. To do this, we used the “planning in advance task” in a virtual environment that constitutes an effective procedure to experimentally evaluate survey maps. With this procedure we present the single case of a woman, with a right medial temporal lobe lesion, who shows a selective impairment in the acquisition of new spatial relationships. The patient’s performance in “planning in advance task” was compared with that of a control group made up of 40 female subjects matched for age and education. Results show how the patient revealed a significantly lower spatial performance when compared to the control group, demonstrating an inability to solve survey-type spatial tasks in complex virtual environments

Paying the circadian toll: The circadian response to LPS injection is dependent on the Toll-like receptor 4

Systemic low doses of the endotoxin lipopolysaccharide (LPS) administered at CT15 (circadian time 12 corresponds to locomotor activity onset) induce phase delays of locomotor activity rhythms in mice. To evaluate if this effect was mediated by the Toll-like receptor 4 (TLR4), our present aim was to characterize the circadian behavior and LPS-induced circadian response of TLR4 (LPS receptor)-deficient mice (in C57bl/10 and C3H backgrounds). In mutants, we observed a free-running period and a light-induced phase delay similar to the one observed in their corresponding wild-type (WT) littermates. The LPS-induced phase delay, wheel running inhibition and c-Fos/Per-1 immunoreactivity in the paraventricular nuclei observed in WT mice was absent or significantly decreased in the TLR4-deficient mice. In conclusion, we show that LPS-induced circadian responses are mediated by TLR4.Fil: Paladino, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Leone, Maria Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Plano, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Golombek, Diego Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentin

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2

A case of pulmonary edema: The critical role of lung-heart integrated ultrasound examination.

Cardiogenic pulmonary edema is a common presentation of acute heart failure normally treated with continuous positive airway pressure (CPAP), diuretics and nitrates. This therapy is contraindicated in case of cardiac tamponade. We describe a case of pulmonary edema due to cardiac tamponade in which integrated lung-heart ultrasound examination allowed prompt diagnosis and pericardiocentesis before administration of CPAP thus avoiding circulatory collapse

The Role of Molecular Chaperones in Virus Infection and Implications for Understanding and Treating COVID-19

The COVID-19 pandemic made imperative the search for means to end it, which requires a knowledge of the mechanisms underpinning the multiplication and spread of its cause, the coronavirus SARS-CoV-2. Many viruses use members of the hosts' chaperoning system to infect the target cells, replicate, and spread, and here we present illustrative examples. Unfortunately, the role of chaperones in the SARS-CoV-2 cycle is still poorly understood. In this review, we examine the interactions of various coronaviruses during their infectious cycle with chaperones in search of information useful for future research on SARS-CoV-2. We also call attention to the possible role of molecular mimicry in the development of autoimmunity and its widespread pathogenic impact in COVID-19 patients. Viral proteins share highly antigenic epitopes with human chaperones, eliciting anti-viral antibodies that crossreact with the chaperones. Both, the critical functions of chaperones in the infectious cycle of viruses and the possible role of these molecules in COVID-19 autoimmune phenomena, make clear that molecular chaperones are promising candidates for the development of antiviral strategies. These could consist of inhibiting-blocking those chaperones that are necessary for the infectious viral cycle, or those that act as autoantigens in the autoimmune reactions causing generalized destructive effects on human tissues

Effects of X-rays on Tuta absoluta for use in inherited sterility programmes

Tuta absoluta is a key pest of tomato crops originating from South America. The consequences of X-radiation on this species were studied under laboratory controlled conditions. The effect of radiation on adult emergence was evaluated exposing male and female pupae to increasing X-rays. Adult emergence decreased as doses of X-radiation increased, with the appearance of deformities such as malformed wings and bent legs at doses C350 Gy. Besides, males and females obtained from irradiated pupae were out crossed with untreated counterparts to explore the effects of X-radiation on inherited sterility. (a) Irradiated male 9 untreated female crosses. Both fecundity and fertility of the untreated females were reduced by radiation, and the effect was stronger as the doses increased. Neither the longevity of parental males and F1 adults nor the sex ratios of the F1 and F2 generations were affected by X-radiation (F1 and F2: first and second generation of descendants of irradiated adults). Inherited sterility effects weremanifested by a significant reduction in the F1 fecundity, F1 fertility, and the amount of larvae and pupae produced. Doses of 200?250 Gy could be used to induce inherited sterility in T. absoluta males. (b) Untreated male 9 irradiated female crosses. The minimum dose at which irradiated females were completely sterile was 200 Gy. The present study is the first study in T. absoluta that provides the starting point for implementing the inherited sterility in this species.Fil: Cagnotti, Cynthia Lorena. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Microbiología y Zoología Agrícola; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Viscarret, Mariana Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Riquelme, Maria B.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Botto, Eduardo Norberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Carabajal Paladino, Leonela Zusel. Instituto Nacional de Tecnología Agropecuaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Segura, Diego Fernando. Instituto Nacional de Tecnología Agropecuaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López, Silvia N.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Microbiología y Zoología Agrícola; Argentin

We are human, they are not: Driving forces behind outgroup dehumanisation and the humanisation of the ingroup

Mostly invigorated by infrahumanisation theory, our knowledge on processes of dehumanisation in intergroup relations has grown considerably in the last decade. Building on these earlier endeavours, the present chapter reviews some recent empirical extensions that highlight the importance of differentiating between ingroup humanisation and outgroup dehumanisation because they are often moderated by specific variables. The role of these separate processes is discussed as a function of the main structural elements that define intergroup behaviour; that is, the defining boundaries of the groups, the relation between the groups at hand, and the ideologies of its members. Finally, the role of the different senses of humanness is discussed, suggesting that the folk conception of humanness differs between cultures

Of precarity and conspiracy: introducing a socio-functional model of conspiracy beliefs

Conspiracy Beliefs (CB) are a key vector of violent extremism, radicalism and unconventional political events. So far, social-psychological research has extensively documented how cognitive, emotional and intergroup factors can promote CB. Evidence also suggests that adherence to CB moves along social class lines: low-income and low-education are among the most robust predictors of CB. Yet, the potential role of precarity—the subjective experience of permanent insecurity stemming from objective material strain—in shaping CB remains largely unexplored. In this paper, we propose for the first time a socio-functional model of CB. We test the hypothesis that precarity could foster increased CB because it undermines trust in government and the broader political ‘elites’. Data from the World Value Survey (n = 21,650; Study 1, electoral CB) and from representative samples from polls conducted in France (n = 1760, Study 2a, conspiracy mentality) and Italy (n = 2196, Study 2b, COVID-19 CB), corroborate a mediation model whereby precarity is directly and indirectly associated with lower trust in authorities and higher CB. In addition, these links are robust to adjustment on income, self-reported SES and education. Considering precarity allows for a truly social-psychological understanding of CB as the by-product of structural issues (e.g. growing inequalities). Results from our socio-functional model suggest that implementing solutions at the socio-economic level could prove efficient in fighting CB