RESUMEN
Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.
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Anopheles , Malaria , Control de Mosquitos , Mosquitos Vectores , Animales , Masculino , Anopheles/genética , Anopheles/fisiología , Mosquitos Vectores/genética , Mosquitos Vectores/parasitología , Malaria/transmisión , Malaria/prevención & control , Femenino , Control de Mosquitos/métodos , Infertilidad Masculina/genética , Sistemas CRISPR-CasRESUMEN
Novel mosquito genetic control tools, such as CRISPR-based gene drives, hold great promise in reducing the global burden of vector-borne diseases. As these technologies advance through the research and development pipeline, there is a growing need for modeling frameworks incorporating increasing levels of entomological and epidemiological detail in order to address questions regarding logistics and biosafety. Epidemiological predictions are becoming increasingly relevant to the development of target product profiles and the design of field trials and interventions, while entomological surveillance is becoming increasingly important to regulation and biosafety. We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided. We intend the software to aid in understanding of human health impacts and biosafety of mosquito genetic control tools, and continue to iterate per feedback from the genetic control community.
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Simulación por Computador , Tecnología de Genética Dirigida , Malaria , Control de Mosquitos , Mosquitos Vectores , Animales , Humanos , Mosquitos Vectores/genética , Control de Mosquitos/métodos , Malaria/epidemiología , Malaria/transmisión , Malaria/prevención & control , Tecnología de Genética Dirigida/métodos , Biología Computacional/métodos , Culicidae/genética , Algoritmos , Enfermedades Transmitidas por Vectores/transmisión , Enfermedades Transmitidas por Vectores/epidemiología , Enfermedades Transmitidas por Vectores/prevención & control , Dinámica PoblacionalRESUMEN
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible-ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii) an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is intended as a resource for both field and computational researchers interested in mosquito gene surveillance.
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Control de Mosquitos , Animales , Control de Mosquitos/métodos , Culicidae/genética , Culicidae/fisiología , Biología Computacional/métodos , Tecnología de Genética Dirigida/métodos , Mosquitos Vectores/genética , Aedes/genética , Resistencia a los Insecticidas/genética , FemeninoRESUMEN
The limited availability of efficient treatments for Candida infections and the increased emergence of antifungal-resistant strains stimulates the search for new antifungal agents. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against Candida albicans, capable of binding mannose-bearing oligosaccharides exposed on the cell surface. This work aimed to investigate the biological and biophysical basis of Helja's binding to C. albicans cell wall mannans and its influence on the fungicidal activity of the lectin. We evaluated the interaction of Helja with the cell wall mannans extracted from the isogenic parental strain (WT) and a glycosylation-defective C. albicans with altered cell wall phosphomannosylation (mnn4∆ null mutants) and investigated its antifungal effect. Helja exhibited stronger antifungal activity on the mutant strain, showing greater inhibition of fungal growth, loss of cell viability, morphological alteration, and formation of clusters with agglutinated cells. This differential biological activity of Helja was correlated with the biophysical parameters determined by solid phase assays and isothermal titration calorimetry, which demonstrated that the lectin established stronger interactions with the cell wall mannans of the mnn4∆ null mutant than with the WT strain. In conclusion, our results provide new evidence on the nature of the Helja molecular interactions with cell wall components, i.e. phosphomannan, and its impact on the antifungal activity. This study highlights the relevance of plant lectins in the design of effective antifungal therapies.
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Antifúngicos , Candida albicans , Pared Celular , Antifúngicos/farmacología , Antifúngicos/química , Candida albicans/efectos de los fármacos , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Lectinas de Plantas/química , Lectinas de Plantas/farmacología , Helianthus/química , Mananos/química , Mananos/farmacología , Mananos/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
Angiogenesis is a crucial process in the progression of various pathologies, like solid tumors, wet age-related macular degeneration, and chronic inflammation. Current anti-angiogenic treatments still have major drawbacks like limited efficacy in diseases that also rely on inflammation. Therefore, new anti-angiogenic approaches are sorely needed, and simultaneous inhibition of angiogenesis and inflammation is desirable. Here, we show that 2-desaza-annomontine (C81), a derivative of the plant alkaloid annomontine previously shown to inhibit endothelial inflammation, impedes angiogenesis by inhibiting CDC2-like kinases (CLKs) and WNT/ß-catenin signaling. C81 reduced choroidal neovascularization in a laser-induced murine in vivo model, inhibited sprouting from vascular endothelial growth factor A (VEGF-A)-activated murine aortic rings ex vivo, and reduced angiogenesis-related activities of endothelial cells in multiple functional assays. This was largely phenocopied by CLK inhibitors and knockdowns, but not by inhibitors of the other known targets of C81. Mechanistically, CLK inhibition reduced VEGF receptor 2 (VEGFR2) mRNA and protein expression as well as downstream signaling. This was partly caused by a reduction of WNT/ß-catenin pathway activity, as activating the pathway induced, while ß-catenin knockdown impeded VEGFR2 expression. Surprisingly, alternative splicing of VEGFR2 was not detected. In summary, C81 and other CLK inhibitors could be promising compounds in the treatment of diseases that depend on angiogenesis and inflammation due to their impairment of both processes.
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Carbolinas , Pirimidinas , Factor A de Crecimiento Endotelial Vascular , beta Catenina , Animales , Humanos , Ratones , Angiogénesis , Inhibidores de la Angiogénesis/farmacología , beta Catenina/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Inflamación , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vía de Señalización WntRESUMEN
Candida glabrata (Nakaseomyces glabrata) is an emergent and opportunistic fungal pathogen that colonizes and persists in different niches within its human host. In this work, we studied five clinical isolates from one patient (P7), that have a clonal origin, and all of which come from blood cultures except one, P7-3, obtained from a urine culture. We found phenotypic variation such as sensitivity to high temperature, oxidative stress, susceptibility to two classes of antifungal agents, and cell wall porosity. Only isolate P7-3 is highly resistant to the echinocandin caspofungin while the other four isolates from P7 are sensitive. However, this same isolate P7-3, is the only one that displays susceptibility to fluconazole (FLC), while the rest of the isolates are resistant to this antifungal. We sequenced the PDR1 gene which encodes a transcription factor required to induce the expression of several genes involved in the resistance to FLC and found that all the isolates encode for the same Pdr1 amino acid sequence except for the last isolate P7-5, which contains a single amino acid change, G1099C in the putative Pdr1 transactivation domain. Consistent with the resistance to FLC, we found that the CDR1 gene, encoding the main drug efflux pump in C. glabrata, is highly overexpressed in the FLC-resistant isolates, but not in the FLC-sensitive P7-3. In addition, the resistance to FLC observed in these isolates is dependent on the PDR1 gene. Additionally, we found that all P7 isolates have a different proportion of cell wall carbohydrates compared to our standard strains CBS138 and BG14. In P7 isolates, mannan is the most abundant cell wall component, whereas ß-glucan is the most abundant component in our standard strains. Consistently, all P7 isolates have a relatively low cell wall porosity compared to our standard strains. These data show phenotypic and genotypic variability between clonal isolates from different niches within a single host, suggesting microevolution of C. glabrata during an infection.
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Antifúngicos , Candida glabrata , Farmacorresistencia Fúngica , Proteínas Fúngicas , Pruebas de Sensibilidad Microbiana , Candida glabrata/genética , Candida glabrata/efectos de los fármacos , Antifúngicos/farmacología , Humanos , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fluconazol/farmacología , Pared Celular/genética , Pared Celular/efectos de los fármacos , Candidiasis/microbiología , Caspofungina/farmacología , Evolución Molecular , Estrés Oxidativo/genética , Equinocandinas/farmacología , Factores de Transcripción/genéticaRESUMEN
The cell membrane protein, dystroglycan, plays a crucial role in connecting the cytoskeleton of a variety of mammalian cells to the extracellular matrix. The α-subunit of dystroglycan (αDG) is characterized by a high level of glycosylation, including a unique O-mannosyl matriglycan. This specific glycosylation is essential for binding of αDG to extracellular matrix ligands effectively. A subset of muscular dystrophies, called dystroglycanopathies, are associated with aberrant, dysfunctional glycosylation of αDG. This defect prevents myocytes from attaching to the basal membrane, leading to contraction-induced injury. Here, we describe a novel Western blot (WB) assay for determining levels of αDG glycosylation in skeletal muscle tissue. The assay described involves extracting proteins from fine needle tibialis anterior (TA) biopsies and separation using SDS-PAGE followed by WB. Glycosylated and core αDG are then detected in a multiplexed format using fluorescent antibodies. A practical application of this assay is demonstrated with samples from normal donors and patients diagnosed with LGMD2I/R9. Quantitative analysis of the WB, which employed the use of a normal TA derived calibration curve, revealed significantly reduced levels of αDG in patient biopsies relative to unaffected TA. Importantly, the assay was able to distinguish between the L276I homozygous patients and a more severe form of clinical disease observed with other FKRP variants. Data demonstrating the accuracy and reliability of the assay are also presented, which further supports the potential utility of this novel assay to monitor changes in âºDG of TA muscle biopsies in the evaluation of potential therapeutics.
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Western Blotting , Distroglicanos , Músculo Esquelético , Distrofia Muscular de Cinturas , Humanos , Distroglicanos/metabolismo , Distrofia Muscular de Cinturas/metabolismo , Distrofia Muscular de Cinturas/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Western Blotting/métodos , Glicosilación , Masculino , FemeninoRESUMEN
The selection of oleaginous bacteria, potentially applicable to biotechnological approaches, is usually carried out by different expensive and time-consuming techniques. In this study, we used Oil Red O (ORO) as an useful dye for staining of neutral lipids (triacylglycerols and wax esters) on thin-layer chromatography plates. ORO could detect minimal quantities of both compounds (detection limit, 0.0025 mg of tripalmitin or 0.005 mg of cetylpalmitate). In addition, we developed a specific, rapid, and inexpensive screening methodology to detect triacylglycerol-accumulating microorganisms grown on the agar plate. This staining methodology detected 9/13 strains with a triacylglycerol content higher than 20% by cellular dry weight. ORO did not stain polyhydroxyalkanoates-producing bacteria. The four oleaginous strains not detected by this screening methodology exhibited a mucoid morphology of their colonies. Apparently, an extracellular polymeric substance produced by these strains hampered the entry of the lipophilic dye into cells. The utilization of the developed screening methodology would allow selecting of oleaginous bacteria in a simpler and faster way than techniques usually used nowadays, based on unspecific staining protocols and spectrophotometric or chromatographic methods. Furthermore, the use of ORO as a staining reagent would easily characterize the neutral lipids accumulated by microorganisms as reserve compounds. KEY POINTS: ⢠Oil Red O staining is specific for triacylglycerols ⢠Oil Red O staining is useful to detect oleaginous bacteria ⢠Fast and inexpensive staining to isolate oleaginous bacteria from the environment.
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Compuestos Azo , Bacterias , Coloración y Etiquetado , Triglicéridos , Cromatografía en Capa Delgada , Coloración y Etiquetado/métodos , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/química , Compuestos Azo/metabolismo , Compuestos Azo/química , Triglicéridos/metabolismo , Triglicéridos/análisis , Técnicas Bacteriológicas/métodosRESUMEN
Imitation that entails faithful reproduction of demonstrated behavior by reenacting a sequence of actions accurately is a fast and efficient way to acquire new skills as well as to conform to social norms. Previous studies reported that both culture and gender might impinge on young children's fidelity of imitation. We analyzed the imitative behavior of 87 children whose ages ranged from 3 to 6 years. An instrumental task was administered that offered partial (opaque apparatus) or total (transparent apparatus) information about causal connection between the demonstrated actions and their effect in achieving a desired reward. Imitative fidelity (imitating the actions that were demonstrated by an adult model yet were unnecessary for achieving the instrumental goal) increased as a function of age in boys, whereas no differences were found in girls. This lack of increase in girls can be ascribed to their displaying higher degrees of imitation fidelity at an earlier age.
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Conducta Imitativa , Motivación , Masculino , Niño , Femenino , Humanos , Preescolar , Normas SocialesRESUMEN
Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.
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Disfunción Cognitiva , Hispánicos o Latinos , Contaminantes Orgánicos Persistentes , Plaguicidas , Bifenilos Policlorados , Humanos , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Disfunción Cognitiva/inducido químicamente , Anciano , Bifenilos Policlorados/sangre , Estados Unidos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Cognición/efectos de los fármacos , Éteres Difenilos Halogenados/sangre , Adulto , Contaminantes Ambientales/sangreRESUMEN
INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.
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INTRODUCTION: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. METHODS: Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence). RESULTS: Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. DISCUSSION: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.
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Envejecimiento Cognitivo , Embarazo , Humanos , Femenino , Salud Reproductiva , Menopausia , Anticonceptivos Orales , HormonasRESUMEN
In May 2022, twelve prickly sharks, Echinorhinus cookei Pietschmann 1928, were sighted at 151-350 m depth in the Cordillera de Coiba seamounts, Pacific Panama. This discovery expands our knowledge of the distribution and habitat use of this rare deep-sea species. It underscores the potential significance of the Cordillera de Coiba seamounts, an offshore marine protected area, as a critical habitat for E. cookei, a species threatened by commercial fishing. Although unverified reports exist on its presence in the tropical eastern Pacific, this publication represents the first documented record of live specimens of E. cookei in Panama.
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Ecosistema , Tiburones , Animales , Panamá , Océano Pacífico , Masculino , Femenino , Distribución AnimalRESUMEN
There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.
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Strains belonging to R. opacus, R. jostii, R. fascians, R. erythropolis and R. equi exhibited differential ability to grow and produce lipids from fruit residues (grape marc and apple pomace), as well as single carbohydrates, such as glucose, gluconate, fructose and sucrose. The oleaginous species, R. opacus (strains PD630 and MR22) and R. jostii RHA1, produced higher yields of biomass (5.1-5.6 g L-1) and lipids (38-44% of CDW) from apple juice wastes, in comparison to R. erythropolis DSM43060, R. fascians F7 and R. equi ATCC6939 (4.1-4.3 g L-1 and less than 10% CDW of lipids). The production of cellular biomass and lipids were also higher in R. opacus and R. jostii (6.8-7.2 g L-1 and 33.9-36.5% of CDW of lipids) compared to R. erythropolis, R. fascians, and R. equi (3.0-3.6 g L-1 and less than 10% CDW of lipids), during cultivation of cells on wine grape waste. A genome-wide bioinformatic analysis of rhodococci indicated that oleaginous species possess a complete set of genes/proteins necessary for the efficient utilization of carbohydrates, whereas genomes from non-oleaginous rhodococcal strains lack relevant genes coding for transporters and/or enzymes for the uptake, catabolism and assimilation of carbohydrates, such as gntP, glcP, edd, eda, among others. Results of this study highlight the potential use of the oleaginous rhodococcal species to convert sugar-rich agro-industrial wastes, such as apple pomace and grape marc, into single-cell oils.
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Frutas , Rhodococcus , Rhodococcus/genética , Rhodococcus/metabolismo , Glucosa/metabolismo , Genómica , Lípidos , Aceites/metabolismoRESUMEN
Background: Chagas cardiomyopathy (CC) increases cardiovascular mortality associated with congestive heart failure (CHF), ventricular arrhythmias (VA), and sudden cardiac death (SCD). Different imaging techniques have been tested to assess disease progression and cardiac risk in individuals with Chagas disease (ChD). In this systematic review, we evaluated the accuracy in detecting cardiac complications in CC patients using cardiac magnetic resonance (CMR) and speckle tracking echocardiography (STE). Methods: A search was done on PubMed, Cochrane, and Embase for studies in humans over 18 years of age with ChD. Demographic data, research methodology, imaging parameters, and cardiac outcomes were extracted, and study quality was assessed, resulting in a narrative description. Results: Twelve studies with 1124 patients were analyzed. One study discovered a contractility pattern by STE. Four studies assessed the identification of Early Cardiac Impairment (ECI) and VA risk, respectively, while three studies evaluated the risk of SCD. Global Longitudinal Strain (GLS) identified patients with ECI (-18.5 ± 3.4% non-fibrosis vs -14.0 ± 5.8% fibrosis, p = 0.006 and -18 ± 2% non-fibrosis vs -15 ± 2% fibrosis, p = 0.004). The amount of fibrosis > 11.78% or in two or more contiguous transmural segments were markers for VA risk. GLS and the amount of fibrosis were found to be predictors of SCD. Conclusions: STE may be considered a screening technique for identifying the subclinical status of CHF. CMR using Late Gadolinium Enhancement (LGE) is considered a relevant parameter for stratifying patients with ChD who are at risk of SCD. Fibrosis and GLS can be used as markers to categorize patients at risk for arrhythmias.
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Chitin is a polymer of N-acetylglucosamine and an essential component of the fungal cell wall. Chitosan is the deacetylated form of chitin and is also important for maintaining the integrity of this structure. Both polysaccharides are widely distributed in nature and have been shown to have a variety of applications in biomedicine, including their potential in immune sensing and as potential antifungal agents. In addition, chitin has been reported to play an important role in the pathogen-host interaction, involving innate and adaptive immune responses. This paper will explore the role of chitin and chitosan when incorporated into nanobiocomposites to improve their efficacy in detecting fungi of medical interest and inhibiting their growth. Potential applications in diagnostic and therapeutic medicine will be discussed, highlighting their promise in the development of more sensitive and effective tools for the early diagnosis of fungal infections. This review aims to highlight the importance of the convergence of nanotechnology and biology in addressing public health challenges.
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Antifúngicos , Quitina , Quitosano , Hongos , Quitina/química , Quitina/farmacología , Quitosano/química , Quitosano/farmacología , Antifúngicos/farmacología , Antifúngicos/química , Hongos/efectos de los fármacos , Hongos/química , Humanos , Nanocompuestos/química , Micosis/inmunología , Micosis/tratamiento farmacológico , Micosis/diagnósticoRESUMEN
Some comparative ontogenetic data imply that effective working-memory capacity develops in ways that are independent of brain size in humans. These are interpreted better from neuroscientific considerations about the continuing development of neuronal architecture in adolescents and young adults, than from one about gross brain mass which already is reached in childhood. By contrast, working-memory capacity in Pan never develops beyond that of three- or four-year-old children. The phylogenetic divergence begs the question of whether it is any longer plausible to infer from the fossil record, that over the past two million years, an ostensibly gradual increase in endocranial volumes, assigned to the genus Homo, can be correlated in a scientifically-meaningful manner with the gradual evolution of our effective executive working memory. It is argued that whereas Pan's effective working-memory capacity is relatively similar to that of its storage working-memory, our working memory is relatively larger with deeper executive control.
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Hominidae , Memoria a Corto Plazo , Niño , Animales , Adulto Joven , Adolescente , Humanos , Preescolar , Memoria a Corto Plazo/fisiología , Filogenia , Hominidae/fisiología , Función Ejecutiva/fisiologíaRESUMEN
A retrospective analysis encompassing 18 yr (1999-2016) of broiler chicken health surveys from broiler production complexes throughout the United States was conducted to identify trends and areas of opportunity. The analysis used necropsy data from 19,577 broiler chickens considered to be "healthy" or "clinically normal" by visual assessment. The very low incidence of dehydrated (0.01%) or undersized (0.02%) broilers is evidence that the objective of examining "healthy" birds was achieved. The results of the correlation analysis were what was expected for "healthy" broilers, with these birds having positive correlations with skin color and size of the bursa of Fabricius. The average age of broilers included in this analysis ranged from 26.2 days in 2008 to 33.7 days in 2013. The percentage of "normal" broilers (those without visible lesions or abnormalities) varied from 5.63% in 2012 to 28.33% in 1999. The results of this study identified four areas of opportunity for improving poultry health: 1) coccidiosis, 2) oral lesions and gizzard erosions, 3) retained yolks, and 4) pododermatitis.
Encuesta retrospectiva sobre la salud de los pollos de engorde: alcance, parámetros y tendencias generales. Se realizó un análisis retrospectivo que abarcó 18 años (1999-2016) de encuestas de salud de pollo de engorde de complejos de producción en los Estados Unidos para identificar tendencias y áreas de oportunidad. El análisis utilizó datos de necropsia de 19,577 pollos de engorde considerados "saludables" o "clínicamente normales" mediante evaluación visual. La incidencia muy baja de pollos de engorde deshidratados (0.01%) o de tamaño pequeño (0.02%) es evidencia de que se logró el objetivo de examinar aves "sanas". Los resultados del análisis de correlación fueron los esperados para pollos de engorde "sanos", ya que estas aves tuvieron correlaciones positivas con el color de la piel y el tamaño de la bolsa de Fabricio. La edad promedio de los pollos de engorde incluidos en este análisis osciló entre 26.2 días en 2008 y 33.7 días en 2013. El porcentaje de pollos de engorde "normales" (aquellos sin lesiones o anomalías visibles) varió del 5.63% en 2012 al 28.33% en 1999. Los resultados de este estudio identificaron cuatro áreas de oportunidad para mejorar la salud de las aves: 1) coccidiosis, 2) lesiones orales y erosiones de la molleja, 3) retención de saco vitelino y 4) pododermatitis.