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1.
Int J Mol Sci ; 24(9)2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37176150

RESUMEN

FoF1-ATP synthases in mitochondria, in chloroplasts, and in most bacteria are proton-driven membrane enzymes that supply the cells with ATP made from ADP and phosphate. Different control mechanisms exist to monitor and prevent the enzymes' reverse chemical reaction of fast wasteful ATP hydrolysis, including mechanical or redox-based blockade of catalysis and ADP inhibition. In general, product inhibition is expected to slow down the mean catalytic turnover. Biochemical assays are ensemble measurements and cannot discriminate between a mechanism affecting all enzymes equally or individually. For example, all enzymes could work more slowly at a decreasing substrate/product ratio, or an increasing number of individual enzymes could be completely blocked. Here, we examined the effect of increasing amounts of ADP on ATP hydrolysis of single Escherichia coli FoF1-ATP synthases in liposomes. We observed the individual catalytic turnover of the enzymes one after another by monitoring the internal subunit rotation using single-molecule Förster resonance energy transfer (smFRET). Observation times of single FRET-labeled FoF1-ATP synthases in solution were extended up to several seconds using a confocal anti-Brownian electrokinetic trap (ABEL trap). By counting active versus inhibited enzymes, we revealed that ADP inhibition did not decrease the catalytic turnover of all FoF1-ATP synthases equally. Instead, increasing ADP in the ADP/ATP mixture reduced the number of remaining active enzymes that operated at similar catalytic rates for varying substrate/product ratios.


Asunto(s)
ATPasas de Translocación de Protón , Protones , ATPasas de Translocación de Protón/metabolismo , Escherichia coli/metabolismo , Hidrólisis , Adenosina Trifosfato
2.
Arch Microbiol ; 204(11): 677, 2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36282427

RESUMEN

Rhipicephalus microplus tick is the ectoparasite causing the greatest economic losses in the livestock industry. Multi-resistance in ticks is increasing, generating the inefficiency of traditional ixodicides, for which biological control has been proposed as an alternative. In this work, we analyze the histomorphological damage caused by the bacterial strain EC-35 on Rhipicephalus microplus. The ixodicidal effect of EC-35 total protein was evaluated on larval or adult ticks comparing with the commercial ixodicide coumaphos 0.02% as a control. Female ticks were processed using the paraffin-embedding technique and stained with hematoxylin-eosin. Also, the pathogenicity of EC-35 was evaluated by capillary feeding and coelom inoculation tests. The identification of the bacterium was performed using the molecular markers 16S RNA and rpoB, by PCR and sequencing technique, and the evolutionary distance was analyzed by Bayesian phylogenetic inference. No differences were observed in the perimeter and area of larvae treated with EC-35 or Coumaphos. The thickness of the integument decreased a 65% with the EC-35 treatment (6.01 ± 0.6 µm) and of 30% in coumaphos (12.04 ± 1.2 µm) in larvae compared with the control group (18.41 ± 2 µm), while no difference was found in adult ticks. The capillary feeding test and coelom inoculation with EC-35 showed an inhibition of reproductive potential of 99.8 ± 7 and an oviposition Inhibition 97 ± 3.02%. The EC-35 strain was genetically related to Serratia marcescens, concluding that these bacteria caused high mortality, oviposition Inhibition, and integument thinning and drastic loss of histoarchitecture in R. microplus tick larvae.


Asunto(s)
Ixodidae , Rhipicephalus , Animales , Femenino , Rhipicephalus/genética , Serratia marcescens/genética , Ixodidae/genética , Filogenia , Cumafos/farmacología , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/farmacología , Teorema de Bayes , Larva , ARN
3.
Int J Mol Sci ; 23(3)2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35163573

RESUMEN

Inflammasomes are multiprotein complexes that represent critical elements of the inflammatory response. The dysregulation of the best-characterized complex, the NLRP3 inflammasome, has been linked to the pathogenesis of diseases such as multiple sclerosis, type 2 diabetes mellitus, Alzheimer's disease, and cancer. While there exist molecular inhibitors specific for the various components of inflammasome complexes, no currently reported inhibitors specifically target NLRP3PYD homo-oligomerization. In the present study, we describe the identification of QM380 and QM381 as NLRP3PYD homo-oligomerization inhibitors after screening small molecules from the MyriaScreen library using a split-luciferase complementation assay. Our results demonstrate that these NLRP3PYD inhibitors interfere with ASC speck formation, inhibit pro-inflammatory cytokine IL1-ß release, and decrease pyroptotic cell death. We employed spectroscopic techniques and computational docking analyses with QM380 and QM381 and the PYD domain to confirm the experimental results and predict possible mechanisms underlying the inhibition of NLRP3PYD homo-interactions.


Asunto(s)
Antiinflamatorios , Proteína con Dominio Pirina 3 de la Familia NLR , Multimerización de Proteína/efectos de los fármacos , Piroptosis/efectos de los fármacos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Células HEK293 , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/química , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo
4.
BMC Infect Dis ; 21(1): 1134, 2021 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-34736397

RESUMEN

BACKGROUND: Amoebiasis is a parasitic disease caused by Entamoeba histolytica, which affects people living in low- and middle-income countries and has intestinal and extraintestinal manifestations. To date, knowledge on coronavirus disease 2019 (COVID-19) coinfection with enteric parasites is limited, and E. histolytica coinfection has not been previously described. Here we present the case of a patient with COVID-19 who, during hospitalisation, presented a clinical picture consistent with an amoebic liver abscess (ALA). CASE PRESENTATION: A 54-year-old man, admitted as a suspected case of COVID-19, presented to our hospital with dyspnoea, malaise, fever and hypoxaemia. A nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction. After 7 days, he developed diarrhoea, choluria and dysentery. An abdominal ultrasound showed a lesion compatible with a liver abscess; stool examination revealed E. histolytica trophozoites, and additional serology for E. histolytica was positive. After 12 days of treatment with metronidazole, ceftazidime and nitazoxanide, the patient reported acute abdominal pain, and an ultrasound examination revealed free liquid in the abdominal cavity. An emergency exploratory laparotomy was performed, finding 3000 mL of a thick fluid described as "anchovy paste". Computed tomography scan revealed a second abscess. He ended up receiving 21 days of antibiotic treatment and was discharged with satisfactory improvement. CONCLUSION: Here we present, to the best of our knowledge, the first report of ALA and COVID-19 co-presenting. Based on their pathophysiological similarities, coinfection with SARS-CoV-2 and E. histolytica could change the patient's clinical course; however, larger studies are needed to fully understand the interaction between these pathogens.


Asunto(s)
COVID-19 , Entamoeba histolytica , Absceso Hepático Amebiano , Humanos , Absceso Hepático Amebiano/diagnóstico , Absceso Hepático Amebiano/tratamiento farmacológico , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , SARS-CoV-2
5.
Rev Med Chil ; 149(7): 1075-1080, 2021 Jul.
Artículo en Español | MEDLINE | ID: mdl-34751310

RESUMEN

The Chilean House of Representatives is discussing the bill on "Dignified death and palliative care", which regulates the so-called medical assistance in dying or euthanasia. This paper will critically analyze the different aspects of the bill, particularly concerning four main dimensions, namely, the patient's condition at the time of requesting euthanasia; the doctor-patient relationship and respect for the autonomy of both parties; the idea of medicine involved in it; and the possible therapeutic alternatives to euthanasia. This critical analysis raises the need to discuss in more depth a project that has to do with such important decisions about our lives and that implies a radical change in the way of thinking and practicing medicine.


Asunto(s)
Eutanasia , Cuidados Paliativos , Chile , Humanos , Relaciones Médico-Paciente
6.
Exp Parasitol ; 218: 107982, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32866584

RESUMEN

Ancylostoma caninum is a gastrointestinal parasite that affect dogs and humans, considered a worldwide public health problem. The control of these parasitosis is increasingly difficult due to the development of multi-drug resistance. Bacillus thuringiensis is an insecticidal, spore forming bacterium, often species specific. The strain GP526 of B. thuringiensis has toxic effect on the cestode Dipylidium caninum and the trematode Centrocestus formosanus, both of them zoonotic parasites. The high degrees of specificity and environment safe make B. thuringiensis suitable for use against pathogen parasites, especially those resistant to synthetic chemical insecticides. The objective of the current work was to evaluate the in vitro effect of B. thuringiensis on Ancylostoma caninum. Spore-crystal mixture of the strains was co-incubated with 120 adult nematodes (males, non-pregnant females and pregnant females) or with 4800 eggs. GP526 showed a nematicidal effect with an LT50 of 35.8 h and an LC50 of 60 µg/ml. It also showed an ovicidal effect with an LC50 of 94.9 µg/ml. Histological analyses showed detachment of the cuticle and of the uterus in adult females, and vacuolization with destruction of the eggs. The effects of GP526 strain were comparable to those of albendazole, allowing us to propose GP526 for A. caninum control, in both, the adult stage at a gastrointestinal level, and in egg stage in the environment. In addition, GP526 can be proposed as a potential broad spectrum antiparasitic drug.


Asunto(s)
Ancylostoma/microbiología , Anquilostomiasis/prevención & control , Bacillus thuringiensis/fisiología , Zoonosis/parasitología , Albendazol/farmacología , Albendazol/uso terapéutico , Ancylostoma/efectos de los fármacos , Animales , Antinematodos/farmacología , Antinematodos/uso terapéutico , Bacillus thuringiensis/química , Proteínas Bacterianas/análisis , Enfermedades de los Perros/parasitología , Perros , Electroforesis en Gel de Poliacrilamida , Femenino , Dosificación Letal Mediana , Masculino , Control Biológico de Vectores/métodos , Zoonosis/prevención & control
7.
Int J Mol Sci ; 21(22)2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33228179

RESUMEN

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.


Asunto(s)
Envejecimiento/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Cannabinoides/uso terapéutico , Hipoglucemiantes/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Envejecimiento/patología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/fisiopatología , Ensayos Clínicos como Asunto , Disfunción Cognitiva/genética , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/prevención & control , Depresión/genética , Depresión/inmunología , Depresión/fisiopatología , Depresión/prevención & control , Suplementos Dietéticos , Microbioma Gastrointestinal/inmunología , Humanos , Inflamación , Resistencia a la Insulina , Síndrome Metabólico/genética , Síndrome Metabólico/inmunología , Síndrome Metabólico/fisiopatología , Síndrome Metabólico/prevención & control , Neuroinmunomodulación/efectos de los fármacos , Estrés Psicológico/genética , Estrés Psicológico/inmunología , Estrés Psicológico/fisiopatología , Estrés Psicológico/prevención & control
8.
Rev Med Chil ; 148(3): 393-398, 2020 Mar.
Artículo en Español | MEDLINE | ID: mdl-32730385

RESUMEN

The catastrophic emergency experienced by many countries with the COVID-19 pandemic emphasized the importance of bioethics for decision-making, both at the public health (equitable and effective policies) and at the clinical level. At the clinical level, the issues are the fulfillment of medical care demand with adequate health care teams, infrastructure, and supplies, and to cover critical care demands that surpass the available resources. Therefore, ethically correct approaches are required for the allocation of life sustaining resources. There are recommendations for the allocating life support during disasters based on multiple considerations, including ethical ones. However, the ethical criteria of existing guidelines are variable. Ethical principles usually considered are saving the greatest number of lives, saving the greatest number of years of life and the principle of the life cycle or the goal to give each individual equal opportunity to live through the various phases of life. However, the centrality of the human being and the search for the common good should be considered. Knowledge of public perspectives and moral benchmarks on these issues is essential. A successful assignment effort will require everyone's trust and cooperation. Decision making should be planned and discussed in advance, since in-depth deliberation will be extremely complex during the disaster. Our goal is to help the health care teams to wisely allocate resources in shortage periods.


Asunto(s)
Toma de Decisiones Clínicas/ética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Asignación de Recursos para la Atención de Salud/ética , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , COVID-19 , Chile/epidemiología , Humanos , Guías de Práctica Clínica como Asunto
9.
Exp Parasitol ; 197: 1-8, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30611101

RESUMEN

Haemonchus contortus is a nematode parasite that establishes in the abomasum of ruminants, it has a cosmopolitan distribution and is a worldwide health problem for livestock. As a first line of defence against parasites, behaviour can help to prevent or fight infection, and may even serve as a method of early presumptive diagnosis. Parasites can affect performance of cattle and cause significant economic losses. The aim of this study was to determine the behavioural and productive changes induced by an experimental infection with H. contortus L3 in bovines. We used 32 dewormed bull calves, randomly divided into two groups, 8 no inoculated controls and 24 that were inoculated with 4000 L3 of H. contortus. Inoculation did not influence haematocrit or haemoglobin values at 0, 28 and 42 days post infection (P> 0.20); however, an increase in the frequency of urination (P = 0.0001) and defecation (P = 0.0001), number of steps (P < 0.001) and self-grooming (P < 0.01) events were observed, even in inoculated animals in which not parasite eggs were found in faeces. During the first 28 days post-inoculation with H. contortus, feedlot performance was not affected (P = 0.16), but during the last 14 days (29-42) inoculated animals gained 15% less weight compared to controls (P = 0.04). Over 42 days, inoculated calves showed a 28% poorer feed efficiency during the 42 days post-inoculation than controls (P < 0.01). Across the experiment, calves inoculated with H. contortus obtained less net energy both for maintenance as for gain from diet (P < 0.01). It is concluded that both, performance and behaviour were modified in feedlot bull-calves parasitized by H. contortus, supporting the practice of deworming when eggs of this parasite are detected in the faeces even in low amounts.


Asunto(s)
Conducta Animal , Enfermedades de los Bovinos/parasitología , Hemoncosis/veterinaria , Anemia/parasitología , Anemia/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/fisiopatología , Enfermedades de los Bovinos/psicología , Dieta/veterinaria , Ingestión de Alimentos , Heces/parasitología , Aseo Animal , Hemoncosis/fisiopatología , Hemoncosis/psicología , Interacciones Huésped-Parásitos , Masculino , Recuento de Huevos de Parásitos/veterinaria , Carga de Parásitos/veterinaria , Distribución Aleatoria , Aumento de Peso
10.
Rev Med Chil ; 146(9): 959-967, 2018 Sep.
Artículo en Español | MEDLINE | ID: mdl-30725015

RESUMEN

BACKGROUND: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. AIM: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. PATIENTS AND METHODS: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. RESULTS: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. CONCLUSIONS: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.


Asunto(s)
Terapia por Ejercicio/métodos , Atención Primaria de Salud , Autocuidado , Dolor de Hombro/rehabilitación , Adolescente , Adulto , Chile , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Evaluación de Programas y Proyectos de Salud , Calidad de Vida , Método Simple Ciego , Encuestas y Cuestionarios , Síndrome , Resultado del Tratamiento
11.
Educ Health (Abingdon) ; 30(1): 11-18, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28707631

RESUMEN

BACKGROUND: Latin America has experienced a tremendous growth in a number of medical schools, and there are concerns about their quality of training in critical areas such as professionalism. Medical professionalism is a cultural construct. The aim of the study was to compare published definitions of medical professionalism from Latin American and non-Latin American regions and to design an original and culturally sound definition. METHODS: A mixed methods approach was used with three phases. First, a systematic search and thematic analysis of the literature were conducted. Second, a Delphi methodology was used to design a local definition of medical professionalism. Third, we used a qualitative approach that combined focus groups and personal interviews with students and deans from four medical schools in Chile to understand various aspects of professionalism education. The data were analyzed using NVivo software. RESULTS: A total of 115 nonrepeated articles were identified in the three databases searched. No original definitions of medical professionalism from Latin America were found. Twenty-six articles met at least one of the three decisional criteria defined and were fully reviewed. Three theoretical perspectives were identified: contractualism, personalism, and deontology. Attributes of medical professionalism were classified in five dimensions: personal, interpersonal, societal, formative, and practical. Participants of the Delphi panel, focus groups, and personal interviews included 36 medical students, 12 faculties, and four deans. They took a personalistic approach to design an original definition of medical professionalism and highlighted the relevance of respecting life, human dignity, and the virtue of prudence in medical practice. Students and scholars differed on the value given to empathy and compassion. DISCUSSION: This study provides an original and culturally sound definition of medical professionalism that could be useful in Latin American medical schools. The methodology used in the study could be applied in other regions as a basis to develop culturally appropriate definitions of medical professionalism.


Asunto(s)
Docentes Médicos , Profesionalismo/normas , Estudiantes de Medicina , Chile , Competencia Clínica/normas , Técnica Delphi , Empatía , Grupos Focales , Humanos , América Latina/etnología , Obligaciones Morales , Profesionalismo/educación , Responsabilidad Social
13.
Heliyon ; 10(10): e31564, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38818186

RESUMEN

A comprehensive analysis is carried out for achieving hygrothermal comfort by using bidirectional heat and mass fluxes between the human skin and its surroundings during cooling seasons, considering the main characteristics of climate, metabolic rate, and clothing fabrics. As hygrothermal comfort is mainly seen as one-direction heat and mass flux from the close surroundings to the human body, without the emitted heat and mass by the human skin, the purpose of the analysis is to find out proper features of the respective clothing fabric according to the inlet boundary conditions, i.e. heat and mass flux from the human body, and the outlet boundary features, i.e. heat and mass flux due to the climate conditions. Thereby, a novel mathematical modelling is developed for heat and mass transfer, respectively. Then, the software Wolfram Mathematica is applied for the numerical solutions of the model. After the model is validated, a sensitivity analysis is carried out. Thereby, it is found that the sensible heat removal by convection, dependent on both airflow and humidity rates, has a great influence on the hygrothermal comfort. Furthermore, solar reflectivity for shortwave radiation, along with longwave radiation from the skin, have influence on the hygrothermal comfort when both ventilation and sweating are set as minimum. Therefore, if the conditions of temperature and relative humidity are proper, both high conductivity and air permeability clothes are recommended. Nevertheless, regarding the reflectivity, it depends on the presence of shortwave radiation, sweating, ventilation, and longwave radiation to consider light-toned or dark colors.

14.
PLoS One ; 19(8): e0307803, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39197020

RESUMEN

Parasites and obesity are health problems worldwide. Rabbits are production animals yielding one of the healthiest meats, also taking advantage of skin, hair, limbs and excreta. It is among the most frequent pets in some countries and widely used as animal model in research. Psoroptes cuniculi is a mite of high transmission rate, affecting welfare and production and obesity causes multiple metabolic, endocrine and immunological disorders, being an emerging problem in domestic animals. Obesity and acarosis are prolonged stressors, modifying the activity of the hypothalamic-pituitary-adrenal axis that can induce metabolic and behavioral disorders. Alterations caused by comorbidities could be similar to or different from those induced by each morbidity separately. We analyzed the influence of obesity on the infection degree with P. cuniculi and on behavior and production. Rabbit does induced to obesity were infected and mated; behaviors in the open field test, obesity estimation indices and productive parameters at delivery and weaning were analyzed. The acarosis induced a decrease in feed intake and a decrease in body weight, a decrease in locomotor, exploratory and chinning behaviors in normal weight and obese does. The infection induced 23% mortality at birth, obesity 45% and comorbidity 74%, while in normal weight rabbits a 6.5% was observed. Weight gain from birth to weaning was lower in the comorbid group, reaching a litter weight of 4.5±0.13 kg in healthy normal weight does and 2.6±0.67 kg in comorbid does. The disturbances induced by the comorbidity were magnified in both behavioral and productive parameters.


Asunto(s)
Conducta Animal , Infestaciones por Ácaros , Obesidad , Psoroptidae , Reproducción , Animales , Conejos , Infestaciones por Ácaros/veterinaria , Femenino , Masculino , Peso Corporal
15.
Artículo en Inglés | MEDLINE | ID: mdl-37779364

RESUMEN

OBJECTIVE: Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD. METHODS: By means of label-free mass spectrometry (MS) and mRNA sequencing (mRNA-seq), we report pre-symptomatic changes in the cortices of TDP-43 and FUS mutant mouse models. Using tissues from transgenic mouse models of mitochondrial diseases as a reference, we performed comparative analyses and extracted unique and common mitochondrial signatures that revealed neuroprotective compensatory mechanisms in response to early damage. RESULTS: In this regard, upregulation of both Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) and mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) were the most representative change in pre-symptomatic ALS/FTD tissues, suggesting that fatty acid beta-oxidation and mitochondrial protein translation are mechanisms of adaptation in response to ALS/FTD pathology. CONCLUSIONS: Together, our unbiased integrative analyses unveil novel molecular components that may influence mitochondrial homeostasis in the earliest phase of ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Enfermedades Mitocondriales , Enfermedades Neurodegenerativas , Enfermedad de Pick , Ratones , Animales , Humanos , Demencia Frontotemporal/metabolismo , Esclerosis Amiotrófica Lateral/patología , Proteómica , Ratones Transgénicos , Perfilación de la Expresión Génica , ARN Mensajero
16.
PeerJ ; 11: e16490, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025673

RESUMEN

The most important fisheries are recording catches below their historical averages despite increased effort. This level of overfishing is worrying and requires the establishment of feasible and precise measures to prevent a continuing decrease in biomass. Determining the factors that lead to changes in the abundance and distribution of overfished resources would allow us to identify the strengths and weaknesses of management schemes; this approach would also make it possible to estimate more accurate parameters for their evaluation. We hypothesize that environmental, temporal, spatial, and operational components contribute to the variation in the relative abundance. Thus, we analyzed the red grouper fishery, the most important demersal fishery in the southeastern Gulf of Mexico (SGM); it is locally known as escama. We employed the catch per unit effort (CPUE) as an index of relative abundance recorded by the semi-industrial fleet (kilogram per effective fishing day) and the small-scale fleet (kilogram per effective fishing hour) during the overexploitation phase (from 1996 to 2019). We fitted several variables of the components using generalized additive models (GAM) and used multi-model inference to determine the best GAM for each fleet. For both fleets, the operational and temporal components (fishing gear and year) have had a greater impact on the distribution and abundance of red grouper in the SGM than the spatial and environmental components (the place of origin and sea surface temperature). These findings encourage the exploration of métier schemes for more efficient fishery management. In addition, we have identified several strategies that would support the recovery of the resource, such as restricting fishing in the quadrants located to the northeast or regulating scuba diving. We recommend that in the future, researchers use the indices we have generated in the present study to evaluate the red grouper fishery.


Asunto(s)
Lubina , Animales , Golfo de México , Conservación de los Recursos Naturales , Explotaciones Pesqueras , Biomasa
17.
bioRxiv ; 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37425781

RESUMEN

Combined multi-omics analysis of proteomics, polar metabolomics, and lipidomics requires separate liquid chromatography-mass spectrometry (LC-MS) platforms for each omics layer. This requirement for different platforms limits throughput and increases costs, preventing the application of mass spectrometry-based multi-omics to large scale drug discovery or clinical cohorts. Here, we present an innovative strategy for simultaneous multi-omics analysis by direct infusion (SMAD) using one single injection without liquid chromatography. SMAD allows quantification of over 9,000 metabolite m/z features and over 1,300 proteins from the same sample in less than five minutes. We validated the efficiency and reliability of this method and then present two practical applications: mouse macrophage M1/M2 polarization and high throughput drug screening in human 293T cells. Finally, we demonstrate relationships between proteomic and metabolomic data are discovered by machine learning.

18.
Curr Biol ; 33(14): 2988-3001.e4, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37490853

RESUMEN

The capacity of beneficial microbes to compete for host infection-and the ability of hosts to discriminate among them-introduces evolutionary conflict that is predicted to destabilize mutualism. We investigated fitness outcomes in associations between legumes and their symbiotic rhizobia to characterize fitness impacts of microbial competition. Diverse Bradyrhizobium strains varying in their capacity to fix nitrogen symbiotically with a common host plant, Acmispon strigosus, were tested in full-factorial coinoculation experiments involving 28 pairwise strain combinations. We analyzed the effects of interstrain competition and host discrimination on symbiotic-interaction outcomes by relativizing fitness proxies to clonally infected and uninfected controls. More than one thousand root nodules of coinoculated plants were genotyped to quantify strain occupancy, and the Bradyrhizobium strain genome sequences were analyzed to uncover the genetic bases of interstrain competition outcomes. Strikingly, interstrain competition favored a fast-growing, minimally beneficial rhizobia strain. Host benefits were significantly diminished in coinoculation treatments relative to expectations from clonally inoculated controls, consistent with competitive interference among rhizobia that reduced both nodulation and plant growth. Competition traits appear polygenic, linked with inter-strain allelopathic interactions in the rhizosphere. This study confirms that competition among strains can destabilize mutualism by favoring microbes that are superior in colonizing host tissues but provide minimal benefits to host plants. Moreover, our findings help resolve the paradox that despite efficient host control post infection, legumes nonetheless encounter rhizobia that vary in their nitrogen fixation.


Asunto(s)
Bradyrhizobium , Fabaceae , Lotus , Rhizobium , Fijación del Nitrógeno , Genotipo , Bradyrhizobium/genética , Simbiosis/genética , Nódulos de las Raíces de las Plantas
19.
Chem Biol Interact ; 382: 110637, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37468116

RESUMEN

This study shows the EDTA-resistant, Ca2+ and Cu2+-dependent hydrolysis of O-hexyl 2,5-dichlorophenyl phosphoramidate (HDCP) compound in reptiles sera determined by spectrophotometry UV/Vis and chiral chromatography. Samples of ten reptile species were incubated with aliquot of 100 or 400 µM HDCP in presence of 100 or 300 µM Cu2+, or 2.5 mM Ca2+ or 5 mM EDTA at 37 °C for 30-60 min. The results shown an activator effect of Cu2+ on HDCP hydrolysis in freshwater turtles sera (Trachemys scripta, Chelydra serpentina and Macrochelys temminckii) because the levels of 2,5-dichlorophenol (DCP; product hydrolysis) were similar (∼37 µM DCP) to chicken serum (positive control group). The marine turtles (Chelonia mydas and Eretmochelys imbricata) and crocodiles (Crocodylusacutus and Crocodylus moreletii) showed ∼50% less HDCPase activity (13-17 µM DCP) compared to the HDCPase activity of the freshwater turtle species. Terrestrial reptile species (snakes and lizards) showed around 25% of activity (7-13 µM DCP) with both copper concentrations. These Cu2+-dependent hydrolysis were stereospecific to R(+)-HDCP (p˂0.05) in the three freshwater turtle species that showed similar hydrolysis to the chicken serum. However, the Ca2+ did not show a significant activating effect on the HDCPase activity (1-8 µM DCP) in any reptile serum. Their hydrolysis levels were very similar to those of EDTA-resistant activity. The present study demonstrates a Cu2+-dependent A-esterase (HDCPase) activity in turtles and points serum albumin as the cuproprotein responsible for this activity, reinforcing its N-terminal sequence (DAEH) as a catalytic center.


Asunto(s)
Cobre , Compuestos Organofosforados , Animales , Hidrólisis , Compuestos Organofosforados/química , Ácido Edético , Pollos , Reptiles
20.
Sci Rep ; 13(1): 12892, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37558726

RESUMEN

La Palma island is located in the NW of the Canary Islands and is one of the most volcanically active of the archipelago, therefore the existence of geothermal resources on the island is highly probable. The main objective of this work is to detect velocity anomalies potentially related to active geothermal reservoirs on La Palma island, by achieving a high-resolution seismic velocity model of the first few kilometres of the crust using Ambient Noise Tomography (ANT). The obtained ANT model is merged with a recent local earthquake tomography model. Our findings reveal two high-velocity zones in the island's northern and southern parts, that could be related to a plutonic intrusion and old oceanic crust materials. Conversely, four low-velocity zones are imaged in the southern part of the island. Two of them can be related to hydrothermal alteration zones located beneath the Cumbre Vieja volcanic complex. This hypothesis is reinforced by comparing the S-wave velocity model with the seismicity recorded during the pre-eruptive phase of the 2021 Tajogaite eruption, which revealed an aseismic volume coinciding with these low-velocity zones. Another low-velocity zone is observed in the southern part of the island, which we interpret as highly fractured rocks which could favour the ascent of hot fluids. A last low-velocity zone is observed in the central part of the island and associated with loose deposits generated by the Aridane valley mega landslide.

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