Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO)

Nitroxyl (HNO) is a biological signaling agent that displays distinctive reactivity compared to nitric oxide (NO). As a consequence, these two reactive nitrogen species trigger different physiological responses. Selective detection of HNO over NO has been a challenge for chemists, and several fluorogenic molecular probes have been recently developed with that goal in mind. Common constructs take advantage of the HNO-induced reduction of Cu(II) to Cu(I). The sensing mechanism of such probes relies on the ability of the unpaired electron in a d orbital of the Cu(II) center to quench the fluorescence of a photoemissive ligand by either an electron or energy transfer mechanism. Experimental and theoretical mechanistic studies suggest that proton-coupled electron transfer mediates this process, and careful tuning of the copper coordination environment has led to sensors with optimized selectivity and kinetics. The current optical probes cover the visible and near-infrared regions of the spectrum. This palette of sensors comprises structurally and functionally diverse fluorophores such as coumarin (blue/green emission), boron dipyrromethane (BODIPY, green emission), benzoresorufin (red emission), and dihydroxanthenes (near-infrared emission). Many of these sensors have been successfully applied to detect HNO production in live cells. For example, copper-based optical probes have been used to detect HNO production in live mammalian cells that have been treated with H2S and various nitrosating agents. These studies have established a link between HSNO, the smallest S-nitrosothiol, and HNO. In addition, a near-infrared HNO sensor has been used to perform multicolor/multianalyte microscopy, revealing that exogenously applied HNO elevates the concentration of intracellular mobile zinc. This mobilization of zinc ions is presumably a consequence of nitrosation of cysteine residues in zinc-chelating proteins such as metallothionein. Future challenges for the optical imaging of HNO include devising probes that can detect HNO reversibly, especially because ratiometric imaging can only report equilibrium concentrations when the sensing event is reversible. Another important aspect that needs to be addressed is the creation of probes that can sense HNO in specific subcellular locations. These tools would be useful to identify the organelles in which HNO is produced in mammalian cells and probe the intracellular signaling networks in which this reactive nitrogen species is involved. In addition, near-infrared emitting probes might be applied to detect HNO in thicker specimens, such as acute tissue slices and even live animals, enabling the investigation of the roles of HNO in physiological or pathological conditions in multicellular systems.National Science Foundation (U.S.)Swiss National Science Foundation (Postdoctoral Fellowship

Counter hegemony, popular education, and resistances: A systematic literature review on the squatters' movement

The squatting movement is a social movement that seeks to use unoccupied land or temporarily or permanently abandoned buildings as farmland, housing, meeting places, or centers for social and cultural purposes. Its main motivation is to denounce and at the same time respond to the economic difficulties that activists believe exist to realize the right to housing. Much of what we know about this movement comes from the informational and journalistic literature generated by actors that are close or even belong to the movement. However, there is also a significant diversity of knowledge and scientific evidence on the squatters' movement that is being produced by academia and that is worth knowing and grouping together. With the aim of defining and understanding how the squatters' movement is constituted and organized, and how it acts, this research analyzes what the scientific literature affirms about it. Through qualitative research based on the systematic literature review (SLR) method, information was sought in the Web of Science (WOS) and Scopus databases. The initial universe of 262 articles was finally reduced to a sample of 32 articles. These have been analyzed by means of a categorized classification content analysis. The results obtained allow us to establish the state of the art on the squatting movement, placing special emphasis on its dynamics of resistance, its process of political subjectivation and its mechanisms of action and self-management. The study suggests that the movement is understood based on collective actions with a political role of resistance to neoliberalism and the inequalities it generates, and of response to the basic and social needs of the communities through self-management

Effects of Chlorpyrifos Over Reproductive Traits of Three Sympatric Freshwater Crustaceans

The exposure to environmentally relevant chlorpyrifos concentrations (0.03, 0.06 and 0.12 µg chlorpyrifos L−1) causes increases in precopulatory guardian behavior time, amplexus reformulation after exposure and in the number of ovigerous females in the amphipod Hyalella curvispina. Effects in incubation period, effective hatching and median lethal concentration on the decapods Macrobrachium borellii and Aegla uruguayana, both in adults and embryos, were achieved at higher concentrations than those found in the environment. Environmentally relevant chlorpyrifos concentrations appear not to affect decapods but several effects in reproductive traits of amphipods were observed.Fil: Negro, Carlos Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Estrubia, J. F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Rivera, F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentin

Spanish expert consensus on the use of safinamide in Parkinson's disease

La safinamida es un nuevo fármaco para el tratamiento de pacientes con enfermedad de Parkinson (EP) con fluctuaciones como tratamiento complementario a levodopa. Dado que por el momento aún no existen estudios de fase IV postautorización debido a la reciente incorporación de la safinamida a la práctica clínica habitual, el interés de este proyecto radica en el desarrollo de una guía de manejo clínico de la safinamida basada en las opiniones de expertos de trastornos del movimiento. Este proyecto se desarrolló en 2 fases: una primera fase que constó de 16 reuniones locales y una segunda fase que consistió en una reunión nacional. Dichas reuniones siguieron un guion de trabajo preestablecido. Tras la reunión nacional se recopilaron las principales conclusiones de los expertos, que han supuesto la base para redactar la presente guía clínica. Se concluyó que la safinamida es eficaz en la reducción de las fluctuaciones motoras y no motoras. Los pacientes con EP con fluctuaciones leves-moderadas son los que más se benefician del tratamiento, si bien el fármaco puede contribuir a mejorar diversos problemas clínicos en pacientes con EP avanzada. Se ha destacado la posibilidad de reducir la dosis de otros fármacos dopaminérgicos tras la introducción de la safinamida, lo cual contribuiría a reducir efectos adversos como el trastorno de control de impulsos. Se hipotetizó sobre el posible efecto de la safinamida sobre la mejoría de las discinesias a dosis más altas de las habitualmente utilizadas. Se ha consensuado que la safinamida es bien tolerada y presenta un perfil de efectos adversos favorable frente a placebo.Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo

Quantitative nanoscale electrostatics of viruses

Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed 29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material.MINECO of Spain through project FIS2011-29493, FIS2014-59562-R, and the Spanish Interdisciplinary Network on the Biophysics of Viruses (Biofivinet, FIS2011-16090-E). CSM acknowledges funding from BFU2013- 41249-P, and Biofivinet. MGM acknowledges funding from the Spanish Government (BIO2012-37649), Comunidad de Madrid (S-505/MAT-0303), and by an institutional grant from Fundación Areces to the Centro de Biología MolecularPeer Reviewe

Directional deep brain stimulation for Parkinson's disease: results of an international crossover study with randomized, double-blind primary endpoint

Objective: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson’s disease. Materials and Methods: Participants received omnidirectional stimulation for the first three months after initial study pro gramming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson’s Disease Rating Scale (UPDRS) part III motor score, and quality of life. Results: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidi rectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. Conclusion: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians

Investigation of gene–environment interactions in relation to tic severit

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investi gated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N=518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-defcit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main efects of the SNPs on tic severity, and the interaction efect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of signifcance (after correcting for multiple testing) in a rep lication sample (N=678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was signifcantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These fndings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies

Caracterización genética y de caracteres reproductivos en variedades de vid sin semilla de Armenia

Trabajo presentado en las IV Jornadas del Grupo de Viticultura de la SECH (Sociedad Española de Ciencias Hortícolas), celebrada en Pamplona (España), los días 26 y 28 de octubre de 2022La apirenia de la mayoría de las variedades comerciales de la vid (Vitis vinifera L.) procede de 'Sultanina', una variedad con origen en Asia Menor. El principal objetivo de este trabajo ha sido la caracterización de posibles fuentes alternativas de apirenia en el germoplasma armenio. Se han estudiado 40 accesiones apirenas de las colecciones armenias de vid en Echmiadzin (ARM006) y en Nalbandyan (ARM011), así como de explotaciones privadas de la región de Armavir (Armenia). El análisis fenotípico de bayas se realizó de acuerdo con los descriptores de la OIV, y el análisis genético mediante el estudio de la mutación causal de apirenia en Sultanina en el gen VviAGL11 y del marcador VviAPT3 ligado al locus del sexo. El análisis de viabilidad y morfología de los granos de polen se visualizó por microscopía óptica y electrónica de barrido. El análisis fenotípico de bayas reveló una amplia variación en el peso de las mismas, así como en la formación de rudimentos seminales. Las flores de nueve cultivares son hermafroditas con un alto nivel de viabilidad del polen. La accesión 'Karmir kishmish' se caracterizó por tener flores funcionalmente femeninas con baja viabilidad de polen y se confirmó genéticamente con VviAPT3. El análisis de microscopía mostró que los granos de polen de las flores hermafroditas tienen forma esferoidal con 3 colporaciones y numerosas perforaciones, mientras que el de la variedad 'Karmir kishmish' es también esferoidal, pero acolporado y con menos perforaciones. El análisis genético reveló que todas las accesiones portan la mutación puntual dominante en VviAGL11 que causa la estenospermocarpia en 'Sultanina'. De hecho, el análisis de 7 marcadores SSR y 48 SNPs demostró que todas son descendientes de la misma. Este estudio confirma que las variedades apirenas armenias descienden de 'Sultanina', y motiva la búsqueda de otros determinantes genéticos que causen variación en el contenido de semillas de las uvas para utilizar como fuentes alternativas en programas de mejora de uva de mesa

Prevalence of Multi-Resistant Microorganisms and Antibiotic Stewardship among Hospitalized Patients Living in Residential Care Homes in Spain: A Cross-Sectional Study

Antimicrobial resistance is a growing global health problem. Patients living in care homes are a vulnerable high-risk population colonized by multidrug-resistant organisms (MDRO). We identified a case series of 116 residents of care homes from a cohort of 540 consecutive patients admitted to the internal medicine service of our hospital. We performed early diagnostic tests of MDRO through anal exudates in our sample. The prevalence of MDRO colonization was 34.5% of residents and 70% of them had not been previously identified in the clinical records. Previous hospitalizations and in-hospital antibiotic administration were significantly associated with the presence of MDRO. Our results emphasize the need to consider care homes in the planning of regional and national infection control measures and for implementing surveillance systems that monitor the spread of antimicrobial resistance in Spain. Systematic early testing upon admission to hospital services with a high prevalence of patients with MDRO colonization (e.g., internal medicine) could contribute to the adoption of adequate prevention measures. Specific educational programs for care home staff should also be implemented to address this increasing problem.Catedra de Docencia e Investigacion SEMERGEN-Medicina de Familia, University of Granada, Spai