Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Vitamin D is an important modulator of the immune response. It acts over several immune cell types where the Vitamin D receptor (VDR) is expressed. Due to the high relevance of this signaling pathway, several studies have investigated the possible influence of genes involved in the metabolism of Vitamin D and its receptor in different human diseases. Here, we analyzed whether four single-nucleotide polymorphisms of the VDR gene (rs731236, rs7975232, rs1544410 and rs2228570) are involved in the susceptibility to infection by Trypanosoma cruzi and/or to chronic Chagas cardiomyopathy (CCC) in a Colombian endemic population for this parasite. Our results showed that the rs2228570*A allele is associated with CCC development (P = 4.46E−03, OR = 1.51). In summary, the data presented in this report suggest that variation within the VDR gene may affect the immune response against T. cruzi, increasing the probability of cardiac complications in infected individuals.Peer reviewe

Vitellogenin Receptor as a Target for Tick Control: A Mini-Review

While much effort has been put into understanding vitellogenesis in insects and other organisms, much less is known of this process in ticks. There are several steps that facilitate yolk formation in developing oocytes of which the vitellogenin receptor (VgR) is a key component. The tick VgR binds vitellogenin (Vg) circulating in the hemolymph to initiate receptor-mediated endocytosis and its transformation into vitellin (Vn). The conversion of Vg into Vn, the final form of the yolk protein, occurs inside oocytes of the female tick ovary. Vn is critical to tick embryos since it serves as the nutritional source for their development, survival, and reproduction. Recent studies also suggest that pathogenic microbes, i.e., Babesia spp., that rely on ticks for propagation and dissemination likely hitchhike onto Vg molecules as they enter developing oocytes through the VgR. Suppressing VgR messenger RNA synthesis via RNA interference (RNAi) completely blocked Babesia spp. transmission into developing tick oocytes, thereby inhibiting vertical transmission of these pathogenic microbes from female to eggs. To date, VgRs from only four tick species, Dermacentor variabilis, Rhipicephalus microplus, Amblyomma hebraeum, and Haemaphysalis longicornis, have been fully sequenced and characterized. In contrast, many more VgRs have been described in various insect species. VgR is a critical component in egg formation and maturation that can serve as a precise target for tick control. However, additional research will help identify unique residues within the receptor that are specific to ticks or other arthropod disease vectors while avoiding cross-reactivity with non-target species. Detailed knowledge of the molecular structure and functional role of tick VgRs will enable development of novel vaccines to control ticks and tick-borne diseases

IL18 Gene Variants Influence the Susceptibility to Chagas Disease

Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.This work is part of the doctoral thesis “Estudio de las bases genéticas de la enfermedad de Chagas” from the Biomedicine PhD program at the Universidad de Granada (Spain).Peer reviewe

Hamiltonian Dynamics of Linearly Polarized Gowdy Models Coupled to Massless Scalar Fields

The purpose of this paper is to analyze in detail the Hamiltonian formulation for the compact Gowdy models coupled to massless scalar fields as a necessary first step towards their quantization. We will pay special attention to the coupling of matter and those features that arise for the three-handle and three-sphere topologies that are not present in the well studied three torus case -in particular the polar constraints that come from the regularity conditions on the metric. As a byproduct of our analysis we will get an alternative understanding, within the Hamiltonian framework, of the appearance of initial and final singularities for these models.Comment: Final version to appear in Classical and Quantum Gravit

Towards a formal description of the collapse approach to the inflationary origin of the seeds of cosmic structure

Inflation plays a central role in our current understanding of the universe. According to the standard viewpoint, the homogeneous and isotropic mode of the inflaton field drove an early phase of nearly exponential expansion of the universe, while the quantum fluctuations (uncertainties) of the other modes gave rise to the seeds of cosmic structure. However, if we accept that the accelerated expansion led the universe into an essentially homogeneous and isotropic space-time, with the state of all the matter fields in their vacuum (except for the zero mode of the inflaton field), we can not escape the conclusion that the state of the universe as a whole would remain always homogeneous and isotropic. It was recently proposed in [A. Perez, H. Sahlmann and D. Sudarsky, "On the quantum origin of the seeds of cosmic structure," Class. Quant. Grav. 23, 2317-2354 (2006)] that a collapse (representing physics beyond the established paradigm, and presumably associated with a quantum-gravity effect a la Penrose) of the state function of the inflaton field might be the missing element, and thus would be responsible for the emergence of the primordial inhomogeneities. Here we will discuss a formalism that relies strongly on quantum field theory on curved space-times, and within which we can implement a detailed description of such a process. The picture that emerges clarifies many aspects of the problem, and is conceptually quite transparent. Nonetheless, we will find that the results lead us to argue that the resulting picture is not fully compatible with a purely geometric description of space-time.Comment: 53 pages, no figures. Revision to match the published versio

Quantum origin of the primordial fluctuation spectrum and its statistics

The usual account for the origin of cosmic structure during inflation is not fully satisfactory, as it lacks a physical mechanism capable of generating the inhomogeneity and anisotropy of our Universe, from an exactly homogeneous and isotropic initial state associated with the early inflationary regime. The proposal in [A. Perez, H. Sahlmann, and D. Sudarsky, Classical Quantum Gravity, 23, 2317, (2006)] considers the spontaneous dynamical collapse of the wave function, as a possible answer to that problem. In this work, we review briefly the difficulties facing the standard approach, as well as the answers provided by the above proposal and explore their relevance to the investigations concerning the characterization of the primordial spectrum and other statistical aspects of the cosmic microwave background and large-scale matter distribution. We will see that the new approach leads to novel ways of considering some of the relevant questions, and, in particular, to distinct characterizations of the non-Gaussianities that might have left imprints on the available data.Comment: 27 pages. Revision to match the published versio

Vitellogenin Receptor as a Target for Tick Control: A Mini-Review

While much effort has been put into understanding vitellogenesis in insects and other organisms, much less is known of this process in ticks. There are several steps that facilitate yolk formation in developing oocytes of which the vitellogenin receptor (VgR) is a key component. The tick VgR binds vitellogenin (Vg) circulating in the hemolymph to initiate receptor-mediated endocytosis and its transformation into vitellin (Vn). The conversion of Vg into Vn, the final form of the yolk protein, occurs inside oocytes of the female tick ovary. Vn is critical to tick embryos since it serves as the nutritional source for their development, survival, and reproduction. Recent studies also suggest that pathogenic microbes, i.e., Babesia spp., that rely on ticks for propagation and dissemination likely “hitchhike” onto Vg molecules as they enter developing oocytes through the VgR. Suppressing VgR messenger RNA synthesis via RNA interference (RNAi) completely blocked Babesia spp. transmission into developing tick oocytes, thereby inhibiting vertical transmission of these pathogenic microbes from female to eggs. To date, VgRs from only four tick species, Dermacentor variabilis, Rhipicephalus microplus, Amblyomma hebraeum, and Haemaphysalis longicornis, have been fully sequenced and characterized. In contrast, many more VgRs have been described in various insect species. VgR is a critical component in egg formation and maturation that can serve as a precise target for tick control. However, additional research will help identify unique residues within the receptor that are specific to ticks or other arthropod disease vectors while avoiding cross-reactivity with non-target species. Detailed knowledge of the molecular structure and functional role of tick VgRs will enable development of novel vaccines to control ticks and tick-borne diseases

Before the Pandemic Ends: Making Sure This Never Happens Again

Introduction On 30 January 2020, the World Health Organization (WHO) declared a Global Health Emergency of international concern attendant to the emergence and spread of SARS-CoV-2, nearly two months after the first reported emergence of human cases in Wuhan, China. In the subsequent two months, global, national and local health personnel and infrastructures have been overwhelmed, leading to suffering and death for infected people, and the threat of socio-economic instability and potential collapse for humanity as a whole. This shows that our current and traditional mode of coping, anchored in responses after the fact, is not capable of dealing with the crisis of emerging infectious disease. Given all of our technological expertise, why is there an emerging disease crisis, and why are we losing the battle to contain and diminish emerging diseases? Part of the reason is that the prevailing paradigm explaining the biology of pathogen-host associations (coevolution, evolutionary arms races) has assumed that pathogens must evolve new capacities - special mutations – in order to colonize new hosts and produce emergent disease (e.g. Parrish and Kawaoka, 2005). In this erroneous but broadly prevalent view, the evolution of new capacities creates new opportunities for pathogens. Further, given that mutations are both rare and undirected, the highly specialized nature of pathogen-host relationships should produce an evolutionary firewall limiting dissemination; by those definitions, emergences should be rare (for a historical review see Brooks et al., 2019). Pathogens, however, have become far better at finding us than our traditional understanding predicts. We face considerable risk space for pathogens and disease that directly threaten us, our crops and livestock – through expanding interfaces bringing pathogens and hosts into increasing proximity, exacerbated by environmental disruption and urban density, fueled by globalized trade and travel. We need a new paradigm that explains what we are seeing. Additional section headers: The Stockholm Paradigm The DAMA Protocol A Sense of Urgency and Long-Term Commitment Reference

Explanatory Model on Academic Self-Efficacy in Engineering Students: Role of Anxiety, Dysthymia, and Negative Affect

Students in engineering tend to be loners, making interpersonal relationships and mental health issues more likely to arise. The COVID pandemic caused university students to experience anxi-ety and depression, which affected their academic performance and self-esteem. However, stu-dents’ mental health was rarely evaluated after the pandemic, especially engineering students, who showed higher levels of depression than students from other disciplines. The present study aims to establish an explanatory model of academic self-efficacy based on factors related to mental health, such as anxiety, depression, and negative emotions. The method used was quan-titative cross-sectional, and a structural equation modeling was used. A sample of 561 students (54.4% males and 45.6% females) was analyzed. Instruments to measure self-efficacy, negative affect, depression, and anxiety, previously validated and with adequate reliability, were applied. The results showed that a state of anxiety affects academic self-efficacy negatively and directly; depression and negative affect indirectly affect academic self-efficacy mediated by a state of anxiety. These results show that a student with depression problems and a predominance of negative emotions is vulnerable to present anxiety in an academic setting. This anxiety causes his efficacy beliefs to decrease. As a result, he does not feel capable of facing academic challenges

The collapse of the wave function in the joint metric-matter quantization for inflation

It has been argued that the standard inflationary scenario suffers from a serious deficiency as a model for the origin of the seeds of cosmic structure: it can not truly account for the transition from an early homogeneous and isotropic stage to another one lacking such symmetries. The issue has often been thought as a standard instance of the "quantum measurement problem", but as has been recently argued by some of us the situation reaches a critical level in the cosmological context of interest here. This has lead to a proposal in which the standard paradigm is supplemented by a hypothesis concerning the self-induced dynamical collapse of the wave function, as representing the physical mechanism through which such change of symmetry is brought forth. This proposal was formulated within the context of semiclassical gravity. Here we investigate an alternative realization of such idea implemented directly within the standard analysis in terms of a quantum field jointly describing the inflaton and metric perturbations, the so called Mukhanov-Sasaki variable. We show that even though the prescription is quite different, the theoretical predictions include some deviations from the standard ones, which are indeed very similar to those found in the early studies. We briefly discuss the differences between the two at both, the conceptual and practical levels.Comment: 31 pages, 6 figures. Replaced to match the published versio