El Moisés de Freud: saber y transmisión en el psicoanálisis

The article examines Freud's text Moses and Monotheism to circumscribe the relation between the presence of the Great Man and the long lasting tradition of Jewish religion. Refers to the emphasis put by Freud in the murder of Moses, since it shows a point where the transmission chain is interrupted. The subject must come in this place of interruption as responsible to give the chain its continuity. The Freudian construction is then approached from the point of view of the psychoanalytical operation when the patient supposes the analyst has full knowledge of the circumstances. It concludes by saying that only when faced with the lack of total knowledge on the part of the analyst which occupies the place of an object that causes the patient desire will the latter recognize a place of his/her own in a chain of transmission.Empezando por el texto Moisés y el monoteísmo, examina las características de la religión judaica en su relación con el Gran Hombre que la inaugura. Reconoce el énfasis dado por Freud al asesinato de Moisés revelando un punto de discontinuidad en la cadena de transmisión. Lugar donde va a ser novedad ver surgir un sujeto que retome la transmisión, sin embargo bajo su propia responsabilidad. Acerca la construcción freudiana de la operación analítica en la cual también se supone que el analista posee saber completo. Concluye que aquel que hace el análisis sólo va a ocupar su posición en una cadena de transmisión cuando se depara con la falta del saber completo del analista, en este momento él va a surgir en la cadena como el sujeto responsable por su duración.Partindo do texto Moisés e o monoteísmo, o artigo examina as características da religião judaica em sua relação com o Grande Homem que a inaugura. Reconhece a ênfase dada por Freud ao assassinato de Moisés, o qual dá relevo a um ponto de descontinuidade na cadeia de transmissão que, remetendo à falha no saber mosaico, indica também o seu lugar de causa da religião judaica; lugar no qual vemos o aspecto inovador de um sujeito que retoma a transmissão, porém, sob sua própria responsabilidade. Em seguida, mostra que esta formulação pode ser aproximada à da operação analítica, pois localiza nesse mesmo lugar o ponto em que, da queda do sujeito a quem se supõe saber, surge o analista em sua dimensão objetal. O analisante responderá à convocação feita pelo analista como objeto, momento em que advirá na cadeia como sujeito responsável por sua duração

Environmental Assessment of Solar Photo-Fenton Processes at Mild Condition in the Presence of Waste-Derived Bio-Based Substances

[EN] The assessment of environmental sustainability has assumed great importance during the study and implementation of a new process, including those aimed to waste valorization and reuse. In this research, the environmental performance of the photo-Fenton processes was evaluated using the life cycle assessment (LCA) methodology. In particular, photo-Fenton conducted in mild conditions (almost neutral pH), using soluble bio-organic substances as auxiliary agents were compared with the "classic" photo-Fenton run at pH 2.8. The evaluation was carried out both, at the laboratory level and at pilot plant scale. LCA analysis shows that working in mild conditions reduces the environmental burden associated with the use of chemicals. On the other hand, the occurring drop in effectiveness significantly increases the overall impact, thus evidencing the need of considering the process as a whole.Costamagna, M.; Arqués Sanz, A.; Lo-Iacono-Ferreira, VG.; Bianco Prevot, A. (2022). Environmental Assessment of Solar Photo-Fenton Processes at Mild Condition in the Presence of Waste-Derived Bio-Based Substances. Nanomaterials. 12(16):1-13. https://doi.org/10.3390/nano12162781113121

Transcriptional Repressors of Fetal Globin Genes as Novel Therapeutic Targets in Beta-Thalassemia

During development the human β-globin gene cluster undergoes two switching processes at the embryo-fetal and fetal-adult stages, respectively, involving changes in chromatin remodeling and in transcriptional regulatory networks. In particular, during the perinatal period, the switch from fetal-to-adult globin gene expression leads to fetal globin genes silencing and progressive decline of fetal hemoglobin (HbF). Impaired hemoglobin switching is associated with hereditary persistence of HbF (HPFH), a condition in which the fetal globin genes fail to be completely silenced in adult red blood cells. This condition, when co-inherited with hemoglobinopathies, has great therapeutic potential because elevated HbF levels can ameliorate β-thalassemia and sickle cell anemia. Therefore, there is a growing interest about the complex network of factors that regulate fetal globin genes expression. Here we discuss the activity of transcriptional repressors of fetal globin genes and their potential role as novel therapeutic targets in β-thalassemia

Antagonizing S1P3 receptor with Cell-Penetrating Pepducins in Skeletal Muscle Fibrosis

Bioactive lipids, derived from the metabolism of plasma membrane, are important mediators of cellular signaling in vertebrates. In recent years there has been a growing interest on sphingosine-1-phosphate (S1P) which is the final metabolite produced during the sequential degradation of plasma membrane glycosphingolipids and sphingomyelin. The S1P acts through five known subtypes of heptameric G-protein coupled receptors (GPCR), namely S1P1-S1P5 (S1PR). Recent evidence indicates that S1P signaling axis contributes to the development and maintenance of the fibrotic process [1]. Fibrosis is a pathological condition that can affect every organ, consequence of a persisting inflammatory and tissue remodeling condition. In different fibrotic models an extensive crosstalk between TGFβ and S1P signaling axis has been demonstrated. S1P3 plays a pivotal role in fibrosis development in different tissues such as skeletal muscle, liver, and kidney [2]. Thus, selective antagonists of the S1P3 receptor could be useful to deeply study its role in fibrosis as well as to develop new therapeutic entities to treat fibrotic diseases. Pepducins specifically target the intracellular loops, acting as allosteric modulators of GPCR activity. Using this approach, we have synthesized a pepducin based S1P3 antagonist namely KRX-725-II (Myristoyl-GRPYDAN-NH2) [3]. Here to improve the S1P1 vs S1P3 selectivity, we have synthesized several derivatives of KRX-725-II pointing our attention on the aromatic residue of the sequence, Tyr4, and with the aim to introduce molecular constraints. The new molecular entities have been evaluated for their selectivity profile by using mouse aortas. This screening allowed us to identify compounds V and VII (embodying respectively L- and D-Tic) as the most selective S1P3 antagonists. The selected compounds also displayed the ability to significantly reduce the profibrotic action of TGFβ1 in C2C12 myoblasts. To explain the higher selectivity observed for compounds V and VII, they were analyzed by Molecular Dynamics (MD) Simulations. The middle conformations of V and VII were compared by superimposing their GRP residues, which adopt a similar backbone orientation (see Figure). This revealed that the DAN residues with β-turn-like motif are located on opposite sides of the plane defined by the L- or D-Tic residue. This difference may explain, in structural terms, the selective S1P3 antagonism of V and VII in comparison to the unselective antagonist KRX-725-II, whose flexibility seems to be high enough for the adaptation to the binding regions of the individual receptor subtypes S1P1 and S1P3. Peptides V and VII possess, indeed, a highly constrained D- or L-Tic residue that hinder the pharmacophore from interacting properly with the binding pocket of the S1P1 receptor, therefore leading to S1P3 selectivity

Antagonizing S1P3 Receptor with Cell-Penetrating Pepducins in Skeletal Muscle Fibrosis

S1P is the final product of sphingolipid metabolism, which interacts with five widely expressed GPCRs (S1P1-5). Increasing numbers of studies have indicated the importance of S1P3 in various pathophysiological processes. Recently, we have identified a pepducin (compound KRX-725-II) acting as an S1P3 receptor antagonist. Here, aiming to optimize the activity and selectivity profile of the described compound, we have synthesized a series of derivatives in which Tyr, in position 4, has been substituted with several natural aromatic and unnatural aromatic and non-aromatic amino acids. All the compounds were evaluated for their ability to inhibit vascular relaxation induced by KRX-725 (as S1P3 selective pepducin agonist) and KRX-722 (an S1P1-selective pepducin agonist). Those selective towards S1P3 (compounds V and VII) were also evaluated for their ability to inhibit skeletal muscle fibrosis. Finally, molecular dynamics simulations were performed to derive information on the preferred conformations of selective and unselective antagonists

An Italian Multicenter Study on the Epidemiology of Respiratory Syncytial Virus During SARS-CoV-2 Pandemic in Hospitalized Children

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged <12 years, admitted for respiratory tract infections from 1 September 2021 to 15 March 2022 in four Italian pediatric hospitals to assess the burden of respiratory viruses during the COVID-19 pandemic in Italy. At admission, a Clinical Respiratory Score was assigned and nasopharyngeal or nasal washing samples were collected and tested for respiratory viruses. Total admissions increased from the second half of October 2021 to the first half of December 2021 with a peak in early November 2021. The respiratory syncytial virus (RSV) incidence curve coincided with the total hospitalizations curve, occurred earlier than in the pre-pandemic years, and showed an opposite trend with respect to the incidence rate of SARS-CoV-2. Our results demonstrated an early peak in pediatric hospitalizations for RSV. SARS-CoV-2 may exhibit a competitive pressure on other respiratory viruses, most notably RSV

The Role of the Parkinson's Disease Gene PARK9 in Essential Cellular Pathways and the Manganese Homeostasis Network in Yeast

YPK9 (Yeast PARK9; also known as YOR291W) is a non-essential yeast gene predicted by sequence to encode a transmembrane P-type transport ATPase. However, its substrate specificity is unknown. Mutations in the human homolog of YPK9, ATP13A2/PARK9, have been linked to genetic forms of early onset parkinsonism. We previously described a strong genetic interaction between Ypk9 and another Parkinson's disease (PD) protein α-synuclein in multiple model systems, and a role for Ypk9 in manganese detoxification in yeast. In humans, environmental exposure to toxic levels of manganese causes a syndrome similar to PD and is thus an environmental risk factor for the disease. How manganese contributes to neurodegeneration is poorly understood. Here we describe multiple genome-wide screens in yeast aimed at defining the cellular function of Ypk9 and the mechanisms by which it protects cells from manganese toxicity. In physiological conditions, we found that Ypk9 genetically interacts with essential genes involved in cellular trafficking and the cell cycle. Deletion of Ypk9 sensitizes yeast cells to exposure to excess manganese. Using a library of non-essential gene deletions, we screened for additional genes involved in tolerance to excess manganese exposure, discovering several novel pathways involved in manganese homeostasis. We defined the dependence of the deletion strain phenotypes in the presence of manganese on Ypk9, and found that Ypk9 deletion modifies the manganese tolerance of only a subset of strains. These results confirm a role for Ypk9 in manganese homeostasis and illuminates cellular pathways and biological processes in which Ypk9 likely functions

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

NURE: An ERC project to study nuclear reactions for neutrinoless double beta decay

Neutrinoless double beta decay (0νββ) is considered the best potential resource to access the absolute neutrino mass scale. Moreover, if observed, it will signal that neutrinos are their own anti-particles (Majorana particles). Presently, this physics case is one of the most important research “beyond Standard Model” and might guide the way towards a Grand Unified Theory of fundamental interactions. Since the 0νββ decay process involves nuclei, its analysis necessarily implies nuclear structure issues. In the NURE project, supported by a Starting Grant of the European Research Council (ERC), nuclear reactions of double charge-exchange (DCE) are used as a tool to extract information on the 0νββ Nuclear Matrix Elements. In DCE reactions and ββ decay indeed the initial and final nuclear states are the same and the transition operators have similar structure. Thus the measurement of the DCE absolute cross-sections can give crucial information on ββ matrix elements. In a wider view, the NUMEN international collaboration plans a major upgrade of the INFN-LNS facilities in the next years in order to increase the experimental production of nuclei of at least two orders of magnitude, thus making feasible a systematic study of all the cases of interest as candidates for 0νββ

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis