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1.
Bioessays ; 45(8): e2200237, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37246937

RESUMEN

Meiotic recombination is one of the main sources of genetic variation, a fundamental factor in the evolutionary adaptation of sexual eukaryotes. Yet, the role of variation in recombination rate and other recombination features remains underexplored. In this review, we focus on the sensitivity of recombination rates to different extrinsic and intrinsic factors. We briefly present the empirical evidence for recombination plasticity in response to environmental perturbations and/or poor genetic background and discuss theoretical models developed to explain how such plasticity could have evolved and how it can affect important population characteristics. We highlight a gap between the evidence, which comes mostly from experiments with diploids, and theory, which typically assumes haploid selection. Finally, we formulate open questions whose solving would help to outline conditions favoring recombination plasticity. This will contribute to answering the long-standing question of why sexual recombination exists despite its costs, since plastic recombination may be evolutionary advantageous even in selection regimes rejecting any non-zero constant recombination.


Asunto(s)
Eucariontes , Recombinación Genética , Estudios Prospectivos , Meiosis/genética , Evolución Biológica , Selección Genética
2.
Proc Natl Acad Sci U S A ; 119(20): e2117440119, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35533277

RESUMEN

Marine traffic is increasing globally yet collisions with endangered megafauna such as whales, sea turtles, and planktivorous sharks go largely undetected or unreported. Collisions leading to mortality can have population-level consequences for endangered species. Hence, identifying simultaneous space use of megafauna and shipping throughout ranges may reveal as-yet-unknown spatial targets requiring conservation. However, global studies tracking megafauna and shipping occurrences are lacking. Here we combine satellite-tracked movements of the whale shark, Rhincodon typus, and vessel activity to show that 92% of sharks' horizontal space use and nearly 50% of vertical space use overlap with persistent large vessel (>300 gross tons) traffic. Collision-risk estimates correlated with reported whale shark mortality from ship strikes, indicating higher mortality in areas with greatest overlap. Hotspots of potential collision risk were evident in all major oceans, predominantly from overlap with cargo and tanker vessels, and were concentrated in gulf regions, where dense traffic co-occurred with seasonal shark movements. Nearly a third of whale shark hotspots overlapped with the highest collision-risk areas, with the last known locations of tracked sharks coinciding with busier shipping routes more often than expected. Depth-recording tags provided evidence for sinking, likely dead, whale sharks, suggesting substantial "cryptic" lethal ship strikes are possible, which could explain why whale shark population declines continue despite international protection and low fishing-induced mortality. Mitigation measures to reduce ship-strike risk should be considered to conserve this species and other ocean giants that are likely experiencing similar impacts from growing global vessel traffic.


Asunto(s)
Tiburones , Animales , Especies en Peligro de Extinción , Plancton , Navíos
3.
Am Nat ; 203(3): E78-E91, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38358806

RESUMEN

AbstractNumerous empirical studies have witnessed an increase in meiotic recombination rate in response to physiological stress imposed by unfavorable environmental conditions. Thus, inherited plasticity in recombination rate is hypothesized to be evolutionarily advantageous in changing environments. Previous theoretical models proceeded from the assumption that organisms increase their recombination rate when the environment becomes more stressful and demonstrated the evolutionary advantage of such a form of plasticity. Here, we numerically explore a complementary scenario-when the plastic increase in recombination rate is triggered by the environmental shifts. Specifically, we assume increased recombination in individuals developing in a different environment than their parents and, optionally, also in offspring of such individuals. We show that such shift-inducible recombination is always superior when the optimal constant recombination implies an intermediate rate. Moreover, under certain conditions, plastic recombination may also appear beneficial when the optimal constant recombination is either zero or free. The advantage of plastic recombination was better predicted by the range of the population's mean fitness over the period of environmental fluctuations, compared with the geometric mean fitness. These results hold for both panmixia and partial selfing, with faster dynamics of recombination modifier alleles under selfing. We think that recombination plasticity can be acquired under the control of environmentally responsive mechanisms, such as chromatin epigenetics remodeling.


Asunto(s)
Evolución Biológica , Recombinación Genética , Humanos , Estrés Fisiológico , Alelos
4.
Small ; : e2405393, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402805

RESUMEN

Engineered poly(vinylidene fluoride) (PVDF) with its diverse crystalline phases plays a crucial role in determining the performance of devices in piezo-, pyro-, ferro- and tribo-electric applications, indicating the importance of distinct phase-detection in defining the structure-property relation. However, traditional characterization techniques struggle to effectively distinguish these phases, thereby failing to offer complete information. In this study, multimodal data-driven techniques have been employed for distinguishing different phases with a machine learning (ML) approach. This developed multimode model has been trained from empirical to theoretical data and demonstrates a classification accuracy of >94%, 15% more noise resilience, and 11% more accuracy from unimodality. Thus, from conception to validation, an alternative approach is provided to autonomously distinguish the different PVDF phases and eschew repetitive experiments that saved resources, thus accelerating the process of materials selection in various applications.

5.
Small ; : e2407318, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367556

RESUMEN

Carbon recycling is poised to emerge as a prominent trend for mitigating severe climate change and meeting the rising demand for energy. Converting carbon dioxide (CO2) into green energy and valuable feedstocks through photocatalytic CO2 reduction (PCCR) offers a promising solution to global warming and energy needs. Among all semiconductors, zinc oxide (ZnO) has garnered considerable interest due to its ecofriendly nature, biocompatibility, abundance, exceptional semiconducting and optical properties, cost-effectiveness, easy synthesis, and durability. This review thoroughly discusses recent advances in mechanistic insights, fundamental principles, experimental parameters, and modulation of ZnO catalysts for direct PCCR to C1 products (methanol). Various ZnO modification techniques are explored, including atomic size regulation, synthesis strategies, morphology manipulation, doping with cocatalysts, defect engineering, incorporation of plasmonic metals, and single atom modulation to boost its photocatalytic performance. Additionally, the review highlights the importance of photoreactor design, reactor types, geometries, operating modes, and phases. Future research endeavors should prioritize the development of cost-effective catalyst immobilization methods for solid-liquid separation and catalyst recycling, while emphasizing the use of abundant and non-toxic materials to ensure environmental sustainability and economic viability. Finally, the review outlines key challenges and proposes novel directions for further enhancing ZnO-based photocatalytic CO2 conversion processes.

6.
Inorg Chem ; 63(5): 2327-2339, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38270093

RESUMEN

As a hydrogen carrier and a vital component in fertilizer production, ammonia (NH3) is set to play a crucial role in the planet's future. While its industrial production feeds half of the global population, it uses fossil fuels and emits greenhouse gases. To tackle this issue, photocatalytic nitrogen fixation using visible light is emerging as an effective alternative method. This strategy avoids carbon dioxide (CO2) emissions and harnesses the largest share of sunlight. In this work, we successfully incorporated a 5-nitro isophthalic acid linker into MOF-808 to introduce structural defects and open metal sites. This has allowed modulation of the electronic structure of the MOF and effectively reduced the band gap energy from 3.8 to 2.6 eV. Combination with g-C3N4 enhanced further NH3 production, as these two materials possess similar band gap energies, and g-C3N4 has shown excellent performance for this reaction. The nitro groups serve as acceptors, and their integration into the MOF structure allowed effective interaction with the free electron pairs on N-(C)3 in the g-C3N4 network nodes. Based on DFT calculations, it was concluded that the adsorption of N2 molecules on open metal sites caused a decrease in their triple bond energy. The modified MOF-808 showed superior performance compared with the other MOFs studied in terms of N2 photoreduction under visible light. This design concept offers valuable information about how to engineer band gap energy in MOF structures and their combination with appropriate semiconductors for solar-powered photocatalytic reactions, such as N2 or CO2 photoreduction.

7.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38892456

RESUMEN

Postoperative pain (POP) is a challenging clinical phenomenon that affects the majority of surgical patients and demands effective management to mitigate adverse outcomes such as persistent pain. The primary goal of POP management is to alleviate suffering and facilitate a seamless return to normal function for the patient. Despite compelling evidence of its drawbacks, opioid analgesia remains the basis of POP treatment. Novel therapeutic approaches rely on multimodal analgesia, integrating different pharmacological strategies to optimize efficacy while minimizing adverse effects. The recognition of the imperative role of the endocannabinoid system in pain regulation has prompted the investigation of cannabinoid compounds as a new therapeutic avenue. Cannabinoids may serve as adjuvants, enhancing the analgesic effects of other drugs and potentially replacing or at least reducing the dependence on other long-term analgesics in pain management. This narrative review succinctly summarizes pertinent information on the molecular mechanisms, clinical therapeutic benefits, and considerations associated with the plausible use of various cannabinoid compounds in treating POP. According to the available evidence, cannabinoid compounds modulate specific molecular mechanisms intimately involved in POP. However, only two of the eleven clinical trials that evaluated the efficacy of different cannabinoid interventions showed positive results.


Asunto(s)
Cannabinoides , Manejo del Dolor , Dolor Postoperatorio , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Cannabinoides/uso terapéutico , Cannabinoides/farmacología , Manejo del Dolor/métodos , Analgesia/métodos , Animales , Analgésicos/uso terapéutico , Analgésicos/farmacología , Endocannabinoides/metabolismo , Endocannabinoides/uso terapéutico
8.
Neuroimage ; 280: 120361, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37669723

RESUMEN

In functional magnetic resonance imaging (fMRI) of the brain the measured signal is corrupted by several (e.g. physiological, motion, and thermal) noise sources and depends on the image acquisition. Imaging at ultrahigh field strength is becoming increasingly popular as it offers increased spatial accuracy. The latter is of particular benefit in brainstem neuroimaging given the small cross-sectional area of most nuclei. However, physiological noise scales with field strength in fMRI acquisitions. Although this problem is in part solved by decreasing voxel size, it is clear that adequate physiological denoising is of utmost importance in brainstem-focused fMRI experiments. Multi-echo sequences have been reported to facilitate highly effective denoising through TE-dependence of Blood Oxygen Level Dependent (BOLD) signals, in a denoising method referred to as multi-echo independent component analysis (ME-ICA). It has not been explored previously how ME-ICA compares to other data-driven denoising approaches at ultrahigh field strength. In the current study, we compared the efficacy of several denoising methods, including anatomical component based correction (aCompCor), Automatic Removal of Motion Artifacts (ICA-AROMA) aggressive and non-aggressive options, ME-ICA, and a combination of ME-ICA and aCompCor. We assessed several data quality metrics, including temporal signal-to-noise ratio (tSNR), delta variation signal (DVARS), spectral density of the global signal, functional connectivity and Shannon spectral entropy. Moreover, we looked at the ability of each method to uncouple the global signal and respiration. In line with previous reports at lower field strengths, we demonstrate that after applying ME-ICA, the data is best post-processed in order to remove spatially diffuse noise with a method such as aCompCor. Our findings indicate that ME-ICA combined with aCompCor and the aggressive option of ICA-AROMA are highly effective denoising approaches for multi-echo data acquired at 7T. ME-ICA combined with aCompCor potentially preserves more signal-of-interest as compared to the aggressive option of ICA-AROMA.


Asunto(s)
Imagen por Resonancia Magnética , Neuroimagen , Humanos , Agresión , Artefactos , Benchmarking
9.
Anal Chem ; 95(19): 7594-7602, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37132509

RESUMEN

Early detection of Alzheimer's disease (AD) is important for taking proper measures against AD pathogenesis. Acetylcholinesterase (AChE) is widely reported to be associated with the pathogenicity of AD. Here, employing the "acetylcholine-mimic" approach, we designed and synthesized a new class of naphthalimide (Naph)-based fluorogenic probes for specific detection of AChE and avoiding interference of butyrylcholinesterase (BuChE), the pseudocholinesterase. We investigated the action of the probes on Electrophorus electricus AChE, and the native human brain AChE that we expressed in Escherichia coli and purified in the active form for the first time. The probe Naph-3 exhibited a substantial fluorescence enhancement with AChE and majorly avoided BuChE. Naph-3 successfully crossed the cell membrane of the Neuro-2a cells and fluoresced upon reaction with endogenous AChE. We further established that the probe could be effectively used for screening AChE inhibitors. Our study provides a new avenue for the specific detection of AChE, which can be extended to the diagnosis of AChE-related complications.


Asunto(s)
Acetilcolinesterasa , Enfermedad de Alzheimer , Humanos , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Acetilcolina , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química
10.
Nat Immunol ; 13(1): 95-102, 2011 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-22101729

RESUMEN

The unique DNA-binding properties of distinct NF-κB dimers influence the selective regulation of NF-κB target genes. To more thoroughly investigate these dimer-specific differences, we combined protein-binding microarrays and surface plasmon resonance to evaluate DNA sites recognized by eight different NF-κB dimers. We observed three distinct binding-specificity classes and clarified mechanisms by which dimers might regulate distinct sets of genes. We identified many new nontraditional NF-κB binding site (κB site) sequences and highlight the plasticity of NF-κB dimers in recognizing κB sites with a single consensus half-site. This study provides a database that can be used in efforts to identify NF-κB target sites and uncover gene regulatory circuitry.


Asunto(s)
Regulación de la Expresión Génica , FN-kappa B/metabolismo , Animales , Secuencia de Bases , Sitios de Unión/genética , Análisis por Conglomerados , ADN/química , ADN/genética , Bases de Datos Genéticas , Humanos , Macrófagos/metabolismo , Ratones , FN-kappa B/genética , Análisis por Matrices de Proteínas , Unión Proteica , Multimerización de Proteína
11.
Inorg Chem ; 62(40): 16451-16463, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37737088

RESUMEN

The S-scheme heterojunction photocatalyst holds potential for better photocatalysis owing to its capacity to broaden the light absorption range, ease electron-hole separation, extend the charge carrier lifespan, and maximize the redox ability. In this study, we integrate zeolitic imidazolate frameworks (ZIFs-67) with the CuFe-LDH composite, offering a straightforward approach towards creating a novel hybrid nanostructure, enabling remarkable performance in both photocatalytic hydrogen (H2) evolution and carbon dioxide (CO2) to methanol (MeOH) conversion. The ZIF-67/CuFe-LDH photocatalyst exhibits an enhanced photocatalytic hydrogen evolution rate of 7.4 mmol g-1 h-1 and an AQY of 4.8%. The superior activity of CO2 reduction to MeOH generation was 227 µmol g-1 h-1 and an AQY of 5.1%, and it still exhibited superior activity after continuously working for 4 runs with nearly negligible decay in activity. The combined spectroscopic analysis, electrochemical study, and computational data strongly demonstrate that this hybrid material integrates the advantageous properties of the individual ZIF-67 and CuFe-LDH exhibiting distinguished photon harvesting, suppression of the photoinduced electron-hole recombination kinetics, extended lifetime, and efficient charge transfer, subsequently boosting higher photocatalytic activities.

12.
Inorg Chem ; 62(22): 8467-8471, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37219484

RESUMEN

The interaction of three free-base meso-tris(p-X-phenyl)corroles H3[TpXPC] (X = H, CH3, OCH3) with Re2(CO)10 at 235 °C in the presence of K2CO3 in o-dichlorobenzene has led to putative rhenium biscorrole sandwich compounds with the formula ReH[TpXPC]2. Density functional theory calculations and Re L3-edge extended X-ray absorption fine structure measurements suggest a seven-coordinate metal center, with the "extra" hydrogen located on one of the corrole nitrogens. The complexes can be deprotonated by a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, resulting in a substantial sharpening of the UV-vis spectra and split Soret bands, consistent with the generation of C2-symmetric anions. Both the seven-coordinate neutral and eight-coordinate anionic forms of the complexes represent a new coordination motif in the field of rhenium-porphyrinoid interactions.

13.
Mol Cancer ; 21(1): 172, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-36045346

RESUMEN

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T cell lymphoma commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK and transcriptionally regulate PDGFRß. Blocking PDGFRß kinase activity with imatinib effectively reduces tumor burden and prolongs survival, although the downstream molecular mechanisms remain elusive. METHODS AND RESULTS: In a transgenic mouse model that mimics PDGFRß-driven human ALCL in vivo, we identify PDGFRß as a driver of aggressive tumor growth. Mechanistically, PDGFRß induces the pro-survival factor Bcl-xL and the growth-enhancing cytokine IL-10 via STAT5 activation. CRISPR/Cas9 deletion of both STAT5 gene products, STAT5A and STAT5B, results in the significant impairment of cell viability compared to deletion of STAT5A, STAT5B or STAT3 alone. Moreover, combined blockade of STAT3/5 activity with a selective SH2 domain inhibitor, AC-4-130, effectively obstructs tumor development in vivo. CONCLUSIONS: We therefore propose PDGFRß as a novel biomarker and introduce PDGFRß-STAT3/5 signaling as an important axis in aggressive ALCL. Furthermore, we suggest that inhibition of PDGFRß or STAT3/5 improve existing therapies for both previously untreated and relapsed/refractory ALK+ ALCL patients.


Asunto(s)
Linfoma Anaplásico de Células Grandes , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Factor de Transcripción STAT3 , Factor de Transcripción STAT5 , Quinasa de Linfoma Anaplásico , Animales , Carcinogénesis/metabolismo , Línea Celular Tumoral , Humanos , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patología , Ratones , Fosforilación , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/farmacología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT5/genética , Transducción de Señal
14.
Acc Chem Res ; 54(15): 3095-3107, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34297542

RESUMEN

Porphyrin chemistry is Shakespearean: over a century of study has not withered the field's apparently infinite variety. Heme proteins continually astonish us with novel molecular mechanisms, while new porphyrin analogues bowl us over with unprecedented optical, electronic, and metal-binding properties. Within the latter domain, corroles occupy a special place, exhibiting a unique and rich coordination chemistry. The 5d metallocorroles are arguably the icing on that cake.New Zealand chemist Penny Brothers has used the word "misfit" to describe the interactions of boron, a small atom with a predilection for tetrahedral coordination, and porphyrins, classic square-planar ligands. Steve Jobs lionized misfits as those who see things differently and push humanity forward. Both perspectives have inspired us. The 5d metallocorroles are misfits in that they encapsulate a large 5d transition metal ion within the tight cavity of a contracted porphyrin ligand.Given the steric mismatch inherent in their structures, the syntheses of some 5d metallocorroles are understandably capricious, proceeding under highly specific conditions and affording poor yields. Three broad approaches may be distinguished.(a) In the metal-alkyl approach, a free-base corrole is exposed to an alkyllithium and the resulting lithio-corrole is treated with an early transition metal chloride; a variant of the method eschews alkyllithium and deploys a transition metal-alkyl instead, resulting in elimination of the alkyl group as an alkane and insertion of the metal into the corrole. This approach is useful for inserting transition metals from groups 4, 5, and, to some extent, 6, as well as lanthanides and actinides.(b) In our laboratory, we have often deployed a low-valent organometallic approach for the middle transition elements (groups 6, 7, 8, and 9). The reagents are low-valent metal-carbonyl or -olefin complexes, which lose one or more carbon ligands at high temperature, affording coordinatively unsaturated, sticky metal fragments that are trapped by the corrole nitrogens.(c) Finally, a metal acetate approach provides the method of choice for gold and platinum insertion (groups 10 and 11).This Account provides a first-hand perspective of the three approaches, focusing on the last two, which were largely developed in our laboratory. In general, the products were characterized with X-ray crystallography, electrochemistry, and a variety of spectroscopic methods. The physicochemical data, supplemented by relativistic DFT calculations, have provided fascinating insights into periodic trends and relativistic effects.An unexpected feature of many 5d metallocorroles, given their misfit character, is their remarkable stability under thermal, chemical, and photochemical stimulation. Many of them also exhibit long triplet lifetimes on the order of 100 µs and effectively sensitize singlet oxygen formation. Many exhibit phosphorescence in the near-infrared under ambient conditions. Furthermore, water-soluble ReO and Au corroles exhibit impressive photocytotoxicity against multiple cancer cell lines, promising potential applications as cancer phototherapeutics. We thus envision a bright future for the compounds as rugged building blocks for new generations of therapeutic and diagnostic (theranostic) agents.


Asunto(s)
Metales/química , Neoplasias/terapia , Fototerapia , Porfirinas/química , Humanos , Ligandos
15.
Phys Chem Chem Phys ; 24(27): 16647-16654, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35766352

RESUMEN

Here, we present double-layer ice confined within various carbon nanotubes (CNTs) using state-of-the-art pressure induced (-5 GPa to 5 GPa) dispersion corrected density functional theory (DFT) calculations. We find that the double-layer ice exhibits remarkably rich and diverse phase behaviors as a function of pressure with varying CNT diameters. The lattice cohesive energies for various pure double layer ice phases follow the order of hexagonal > pentagonal > square tube > hexagonal-close-packed (HCP) > square > buckled-rhombic (b-RH). The confinement width was found to play a crucial role in the square and square tube phases in the intermediate pressure range of about 0-1 GPa. Unlike the phase transition in pure bilayer ice structures, the relative enthalpies demonstrate that the pentagonal phase, rather than the hexagonal structure, is the most stable ice polymorph at ambient pressure as well as in a deep negative pressure region, whereas the b-RH phase dominates under high pressure. The relatively short O⋯O distance of b-RH demonstrates the presence of a strong hydrogen bonding network, which is responsible for stabilizing the system.

16.
Int J Mol Sci ; 23(18)2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36142488

RESUMEN

The objectives of this study were to identify genetic loci in the bread wheat genome that would influence yield stability and quality under water stress, and to identify accessions that can be recommended for cultivation in dry and hot regions. We performed a genome-wide association study (GWAS) using a panel of 232 wheat accessions spanning diverse ecogeographic regions. Plants were evaluated in the Israeli Northern Negev, under two environments: water-limited (D; 250 mm) and well-watered (W; 450 mm) conditions; they were genotyped with ~71,500 SNPs derived from exome capture sequencing. Of the 14 phenotypic traits evaluated, 12 had significantly lower values under D compared to W conditions, while the values for two traits were higher under D. High heritability (H2 = 0.5-0.9) was observed for grain yield, spike weight, number of grains per spike, peduncle length, and plant height. Days to heading and grain yield could be partitioned based on accession origins. GWAS identified 154 marker-trait associations (MTAs) for yield and quality-related traits, 82 under D and 72 under W, and identified potential candidate genes. We identified 24 accessions showing high and/or stable yields under D conditions that can be recommended for cultivation in regions under the threat of global climate change.


Asunto(s)
Estudio de Asociación del Genoma Completo , Triticum , Pan , Grano Comestible/genética , Genómica , Fenotipo , Sitios de Carácter Cuantitativo , Triticum/genética
17.
Int J Mol Sci ; 23(9)2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35563156

RESUMEN

The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.


Asunto(s)
Trastornos Mentales , Esquizofrenia , Animales , Biomarcadores , Endocannabinoides/fisiología , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/genética , Trastornos del Humor , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética
18.
Plant J ; 101(3): 555-572, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31571297

RESUMEN

Dissection of the genetic basis of wheat ionome is crucial for understanding the physiological and biochemical processes underlying mineral accumulation in seeds, as well as for efficient crop breeding. Most of the elements essential for plants are metals stored in seeds as chelate complexes with phytic acid or sulfur-containing compounds. We assume that the involvement of phosphorus and sulfur in metal chelation is the reason for strong phenotypic correlations within ionome. Adjustment of element concentrations for the effect of variation in phosphorus and sulfur seed content resulted in drastic change of phenotypic correlations between the elements. The genetic architecture of wheat grain ionome was characterized by quantitative trait loci (QTL) analysis using a cross between durum and wild emmer wheat. QTL analysis of the adjusted traits and two-trait analysis of the initial traits paired with either P or S considerably improved QTL detection power and accuracy, resulting in the identification of 105 QTLs and 617 QTL effects for 11 elements. Candidate gene search revealed some potential functional associations between QTLs and corresponding genes within their intervals. Thus, we have shown that accounting for variation in P and S is crucial for understanding of the physiological and genetic regulation of mineral composition of wheat grain ionome and can be implemented for other plants.


Asunto(s)
Fósforo/metabolismo , Sitios de Carácter Cuantitativo/genética , Azufre/metabolismo , Triticum/genética , Cruzamiento , Grano Comestible , Fenotipo , Semillas/genética , Semillas/fisiología , Triticum/fisiología
19.
J Nutr ; 151(6): 1646-1655, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33758915

RESUMEN

BACKGROUND: School-based iron and folic acid (IFA) supplementation is recommended for adolescent girls in countries with high burdens of anemia. OBJECTIVES: We aimed to evaluate the context-specific effectiveness of a school-based, integrated anemia control program with IFA supplementation in Ghana. METHODS: Using data from a pre-post, longitudinal program evaluation, we evaluated the effectiveness of school-based weekly IFA supplementation in reducing the burden of anemia and increasing hemoglobin concentrations (Hb; primary outcomes) in 2 regions of Ghana. Generalized linear mixed effects models with schools (clusters) as random effects were used to quantify the change in the anemia prevalence and the mean Hb associated with cumulative IFA tablet consumption over 1 school year (30-36 weeks), controlling for participant-level potential confounders. A cut point for minimum effective cumulative IFA consumption that is reflective of adequate Hb was derived following logistic regression. This cut point was verified by a restricted cubic spline model of IFA consumption and Hb. RESULTS: The analytical sample included 60 schools and 1387 girls ages 10-19 years. The prevalence of anemia declined during 1 school year of the intervention, from 25.1% to 19.6% (P = 0.001). Students consumed a mean of 16.4 IFA tablets (range, 0-36). IFA consumption was positively associated with Hb and negatively associated with anemia. Each additional IFA tablet consumed over the school year was associated with a 5% (95% CI, 1-10%) reduction in the adjusted odds of anemia at follow-up, though the relationship is nonlinear. The cut point for minimum effective consumption was 26.7 tablets over a 30-36-week school year, with tablets provided weekly. CONCLUSIONS: School-based weekly IFA supplementation is effective in improving Hb and reducing the anemia prevalence among schoolgirls in Ghana, though most participants consumed fewer than the minimum effective number of IFA tablets. Increasing intake adherence may further improve anemia outcomes in this population.


Asunto(s)
Anemia Ferropénica , Anemia , Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Hierro/administración & dosificación , Adolescente , Anemia/epidemiología , Anemia/prevención & control , Anemia Ferropénica/epidemiología , Anemia Ferropénica/prevención & control , Niño , Femenino , Ghana/epidemiología , Hemoglobinas/análisis , Humanos , Estudios Longitudinales , Estudios Prospectivos , Instituciones Académicas , Adulto Joven
20.
Heredity (Edinb) ; 127(3): 278-287, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34163036

RESUMEN

Environmental seasonality is a potent evolutionary force, capable of maintaining polymorphism, promoting phenotypic plasticity and causing bet-hedging. In Drosophila, environmental seasonality has been reported to affect life-history traits, tolerance to abiotic stressors and immunity. Oscillations in frequencies of alleles underlying fitness-related traits were also documented alongside SNPs across the genome. Here, we test for seasonal changes in two recombination characteristics, crossover rate and crossover interference, in a natural D. melanogaster population from India using morphological markers of the three major chromosomes. We show that winter flies, collected after the dry season, have significantly higher desiccation tolerance than their autumn counterparts. This difference proved to hold also for hybrids with three independent marker stocks, suggesting its genetic rather than plastic nature. Significant between-season changes are documented for crossover rate (in 9 of 13 studied intervals) and crossover interference (in four of eight studied pairs of intervals); both single and double crossovers were usually more frequent in the winter cohort. The winter flies also display weaker plasticity of both recombination characteristics to desiccation. We ascribe the observed differences to indirect selection on recombination caused by directional selection on desiccation tolerance. Our findings suggest that changes in recombination characteristics can arise even after a short period of seasonal adaptation (~8-10 generations).


Asunto(s)
Drosophila melanogaster , Drosophila , Adaptación Fisiológica , Animales , Drosophila melanogaster/genética , Recombinación Genética , Estaciones del Año
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