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1.
bioRxiv ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39026891

ABSTRACT

Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and neuro-inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that might be expected to alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction and related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, and repetitive behaviors and sensory over-responsivity in adult offspring with persistent brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-,ion channel-, and epilepsy-associated genes, in the same time frame. Our findings suggest that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction, including neuronal excitability, altered gene expression in multiple cell types, sensory functional network connectivity, and modulation of information flow. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD behaviors in adult animals without requiring long-term physical alterations to the brain. Thus, restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing both primary sensory and social behavior phenotypes, and compensatory repetitive behavior phenotypes.

2.
Braz. j. biol ; 84: e257739, 2024. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1355883

ABSTRACT

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.


Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.


Subject(s)
Salicylic Acid/pharmacology , Solanum melongena/metabolism , Photosynthesis , Stress, Physiological , Plant Leaves/metabolism , Seedlings , Salinity , Salt Tolerance , Antioxidants/metabolism
3.
Braz. j. biol ; 842024.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469330

ABSTRACT

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.


Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

4.
Biosystems ; 232: 105005, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37611860

ABSTRACT

We propose a theoretical model to investigate the thermodynamics of single and coupled two-state ion channels, associated with mechanoelectrical transduction (MET) and hair cell biophysics. The modeling was based on the Tsallis nonextensive statistical mechanics. The choice for a nonextensive framework in modeling ion channels is encouraged on the fact that we take into account the presence of interactions or long-range correlations in the dynamics of single and coupled ion channels. However, the basic assumptions that support Boltzmann-Gibbs statistics, traditionally used to model ion channel dynamics, state that the system is formed by independent or weakly interacting elements. Despite being well studied in many biological systems, the literature has not yet addressed the study of both entropy and mutual information related to isolated or physically interacting pairs of MET channels. Inspired by hair cell biophysics, we show how the presence of nonextensivity, or subadditivity and superadditivity modulates the nonextensive entropy and mutual information as functions of stereocilia displacements. We also observe that the magnitude of the interaction between the two channels, given by a nonextensive parameter, influences the amplitude of the nonextensive joint entropy and mutual information as functions of the hair cell displacements. Finally, we show how nonextensivity regulates the current versus displacement curve for a single and a pair of interacting two-state channels. The present findings shed light on the thermodynamic process involved in the molecular mechanisms of the auditory system.


Subject(s)
Hair Cells, Auditory , Ion Channels , Biophysics , Entropy , Transducers
5.
Braz J Biol ; 83: e273414, 2023.
Article in English | MEDLINE | ID: mdl-37283339

ABSTRACT

Sugarcane cultivation stands out in Brazilian agribusiness, covering more than eight million hectares for the production of sugar, ethanol, and by-products. Fertilization is one of the limiting factors in sugarcane yield, for which filter cake is a viable solution to meet plant nutritional needs. This study aimed to assess the effect of enriched filter cake on gas exchange and yield in RB041443 sugarcane, cultivated in soils of the coastal tablelands of Paraíba, Brazil. The experiment was conducted in the Monte Alegre S/A sugarcane mill, in the municipality of Mamanguape, using a randomized blocks experimental design, with 12 treatments (T1- cake, T2- cake + MAP, T3- cake + gypsum, T4 - cake + phosphate, T5- cake + bagasse, T6- cake + MAP + gypsum, T7- cake + MAP + phosphate, T8- cake + MAP + bagasse, T9- cake + gypsum + phosphate, T10- cake + gypsum + bagasse, T11- cake + phosphate + bagasse, and T12- control (only MAP)), and 4 replications, totaling 48 plots. A significant effect (5% probability) was also observed for the variables number of leaves and tons of stem per hectare (TSH). T1- cake, T4- cake + phosphate, T6- cake + MAP + gypsum and T10- cake + gypsum + bagasse, had the best results for TSH, with yields greater than 140 t ha-1. Regarding stomatal conductance, the highest values were obtained in T6 and T8, which, together with T11, had the highest gs values. Concerning the internal carbon concentration, T1, T2, T6, and T8 stood out. T6 also had a significant effect on transpiration. From this study, it was concluded that the use of enriched filter cake as a base fertilizer in sugarcane culture contributes to increasing the yield of the RB041443 variety, generating positive responses for plant gas exchange, being T1 and T10 indicated to increase the production in the sugar-energy sector.


Subject(s)
Saccharum , Calcium Sulfate , Edible Grain , Phosphates , Sugars , Thyrotropin
6.
Braz J Biol ; 84: e257739, 2022.
Article in English | MEDLINE | ID: mdl-35081218

ABSTRACT

Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.


Subject(s)
Salicylic Acid , Solanum melongena , Antioxidants/metabolism , Photosynthesis , Plant Leaves/metabolism , Salicylic Acid/pharmacology , Salinity , Salt Tolerance , Seedlings , Solanum melongena/metabolism , Stress, Physiological
7.
Eur Cell Mater ; 42: 196-219, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34613611

ABSTRACT

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients' life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Extracellular Matrix , Humans , Intervertebral Disc Degeneration/therapy , Regenerative Medicine , Tissue Engineering
8.
Opt Lett ; 46(16): 3905-3908, 2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34388771

ABSTRACT

Light scattering by disordered media is a ubiquitous effect. After passing through them, the light acquires a random phase, masking or destroying associated information. Filtering this random phase is of paramount importance to many applications, such as sensing, imaging, and optical communication, to cite a few, and it is commonly achieved through computationally extensive post-processing using statistical correlation. In this work, we show that mixing noisy optical modes of various complexity in a second-order nonlinear medium can be used for efficient and straightforward filtering of a random wavefront under sum-frequency generation processes without utilizing correlation-based calculations.

9.
Arq. bras. med. vet. zootec. (Online) ; 73(2): 361-366, Mar.-Apr. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1248924

ABSTRACT

We investigated the local and systemic effects of hyperbaric oxygen therapy in BALB/C mice, exposed to two different exposure times, under 2.4 atmosphere (ATM). Fifteen animals were divided into three groups (GI, GII and Control) and underwent a surgical excision of a skin fragment of approximately one square centimeter of the dorsal region. The wounds were treated and monitored for 21 days. In the control group, the wound was cleaned once a day with sterile 0.9% NaCl solution. GI and GII mice were submitted to daily hyperbaric oxygen therapy of 30 or 60minutes sessions, respectively. The wounds were photographed every three days and their surfaces were analyzed by an image analyzer. At 21 days, all animals were euthanatized for histopathological analysis of the skin, lungs and liver in order to identify eventual alterations in wound healing or in the analyzed organs. Animals belonging to GI showed a faster skin wound healing in comparison to the other groups. Animals from GII, however, showed a delayed wound healing process and exhibited lung and microcirculatory alterations. These findings allow us to conclude that the exposure time to the oxygen in hyperbaric environment is crucial and can help or disturb skin wound healing or even be deleterious to other organs.(AU)


Investigaram-se os efeitos locais e sistêmicos da oxigenoterapia hiperbárica em camundongos BALB / C, submetidos a dois tempos de exposição diferentes, sob atmosfera 2,4 (ATM). Quinze animais foram divididos em três grupos (GI, GII e controle) e submetidos à excisão cirúrgica de fragmento de pele de aproximadamente um centímetro quadrado da região dorsal. As feridas foram tratadas e acompanhadas por 21 dias. No grupo controle, a ferida foi limpa uma vez ao dia, com solução estéril de NaCl 0,9%. Camundongos GI e GII foram submetidos à oxigenoterapia hiperbárica diária de 30 ou 60 minutos de sessões, respectivamente. As feridas foram fotografadas a cada três dias, e suas superfícies analisadas por um analisador de imagens. Aos 21 dias, todos os animais foram submetidos à eutanásia para análise histopatológica da pele, do pulmão e do fígado, em busca de eventuais alterações na cicatrização da ferida ou nos órgãos analisados. Animais pertencentes ao GI apresentaram cicatrização mais rápida de feridas cutâneas em comparação aos outros grupos. Já os animais do GII apresentaram retardo na cicatrização da ferida e alterações pulmonares e microcirculatórias. Esses achados permitem concluir que o tempo de exposição ao oxigênio em ambiente hiperbárico é fundamental e pode auxiliar ou atrapalhar a cicatrização de feridas cutâneas ou mesmo ser deletério para outros órgãos.(AU)


Subject(s)
Animals , Mice , Degloving Injuries/therapy , Hyperbaric Oxygenation/methods , Hyperbaric Oxygenation/veterinary , Wound Healing
10.
Eur Biophys J ; 49(7): 571-589, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32939610

ABSTRACT

Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, ß, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-ß-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and ß-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.


Subject(s)
Cannabidiol/chemistry , Cyclodextrins/chemistry , Algorithms , Computer Simulation , Dronabinol/chemistry , Entropy , Lactic Acid/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Poisson Distribution , Solubility , Temperature , Thermodynamics , Water
11.
Health Educ Res ; 35(5): 396-406, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32772070

ABSTRACT

Effective obesity interventions in adolescent populations have been identified as an immediate priority action to stem the increasing prevalence of adult obesity. The purpose of this meta-analysis was to make a quantitative analysis of the impact of school-based interventions on body mass index during adolescence. Studies were retrieved from PubMed, Scopus, Science Direct and Web of Science databases. Results were pooled using a random-effects model with 95% confidence interval considered statistically significant. Of the 18 798 possible relevant articles identified, 12 articles were included in this meta-analysis. The global result showed a low magnitude effect, though it was statistically significant (N = 14 428), global e.s. = -0.055, P = 0.004 (95% CI = -0.092, -0.017). Heterogeneity was low among the studies (I2 = 9.017%). The funnel plot showed no evidence of publication bias. The rank-correlation test of Begg (P = 0.45641) and Egger's regression (P = 0.19459) confirmed the absence of bias. This meta-analysis reported a significant effect favoring the interventions; however, future research are needed since the reported the evidence was of low magnitude, with the studies following a substantial range of approaches and mostly had a modest methodological quality.


Subject(s)
Schools , Adolescent , Body Mass Index , Humans , Prevalence
12.
Opt Lett ; 45(14): 4064-4067, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32667355

ABSTRACT

By considering parity-defined Laguerre-Gaussian (LG) and Hermite-Gaussian (HG) beams as input modes, we present arguments through experimental and theoretical results in order to affirm that using HG modes as bases is more suitable for optical mode conversion than using LG modes. By analyzing the normalized overlap integral and the generated modes, we determine a clear rule for the dominant mode for nonlinear mixing of HG beams, while the same is not possible for LG beams. In addition, examples of optical modal conversion using both HG and LG modes as input beams are demonstrated.

13.
Trauma Case Rep ; 27: 100298, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32420441

ABSTRACT

Spinal trauma is rare in children, but when it occurs, trauma of the cervical spine corresponds to 60%-80% of all cases. The most common causes of pediatric cervical spine injuries are automobile accidents, sports activities, and leisure-related accidents. Herein we report a surgically-treated case of cervical spine trauma with fractures of multiple vertebrae. A 12-year-old female victim of a high fall (from a tree) was admitted to the emergency room with neck pain and weakness in all the limbs. On examination, she was conscious, breathing spontaneously, with grade-4 tetraparesis, and preserved sphincter control. Cervical spine computed tomography (CT) revealed a burst fracture of the C4 body with retropulsion into the spinal cord and fractures of the C5 body and posterior elements of C2, C3, and C4. Cervical spine magnetic resonance imaging (MRI) revealed a hypersignal of the spinal cord from C3 to C6 in T2, indicating contusion. Because no signs of posterior spine instability (ligament lesions) were noted on MRI, we decided to perform a C3-C5 anterior arthrodesis with C4 corpectomy and autologous (iliac) graft placement. The patient had a good postoperative evolution. Furthermore, the patient had no motor deficit, but due to the other fractures in the spine, we chose to keep the cervical collar for 3 months and followed-up on an outpatient basis. Although spinal trauma is less frequent in children than in adults, children can have severe cervical spine injuries (multiple fractures with spinal contusion), and then surgery plays a key role in stabilizing the spine and decompressing the spinal cord to avoid sequelae.

14.
J Biol Phys ; 44(4): 539-556, 2018 12.
Article in English | MEDLINE | ID: mdl-29974373

ABSTRACT

Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17ß-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.


Subject(s)
Estradiol/metabolism , Estrogens/metabolism , Glucose/metabolism , Sex Hormone-Binding Globulin/metabolism , Electrolytes , Estradiol/chemistry , Estrogens/chemistry , Humans , Molecular Dynamics Simulation , Protein Conformation , Sex Hormone-Binding Globulin/chemistry
15.
Nat Commun ; 9(1): 2250, 2018 06 08.
Article in English | MEDLINE | ID: mdl-29884780

ABSTRACT

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Motor Cortex/physiopathology , Motor Neurons/physiology , Neuronal Plasticity/physiology , Recovery of Function/physiology , Stroke/physiopathology , Animals , Brain Mapping , Cyclic AMP Response Element-Binding Protein/genetics , Gene Expression Profiling , Male , Mice, Inbred C57BL , Motor Cortex/metabolism , Motor Neurons/metabolism , Neuronal Plasticity/genetics , Patch-Clamp Techniques , Stroke/genetics
16.
Neurobiol Learn Mem ; 153(Pt A): 21-25, 2018 09.
Article in English | MEDLINE | ID: mdl-29496645

ABSTRACT

Memories are dynamic in nature. A cohesive representation of the world requires memories to be altered over time, linked with other memories and eventually integrated into a larger framework of sematic knowledge. Although there is a considerable literature on how single memories are encoded, retrieved and updated, little is known about the mechanisms that govern memory linking, e.g., linking and integration of various memories across hours or days. In this review, we present evidence that specific memory allocation mechanisms, such as changes in CREB and intrinsic excitability, ensure memory storage in ways that facilitate effective recall and linking at a later time. Beyond CREB and intrinsic excitability, we also review a number of other phenomena with potential roles in memory linking.


Subject(s)
Brain/physiology , Cyclic AMP Response Element-Binding Protein/physiology , Memory/physiology , Mental Recall/physiology , Neurons/physiology , Animals , Cortical Excitability , Humans , Neuronal Plasticity , Synapses/physiology , Time Factors
17.
J Biol Phys ; 44(1): 51-52, 2018 03.
Article in English | MEDLINE | ID: mdl-29181685

ABSTRACT

The authors apologize for the following errors published in the article. However, these errors do not modify the main assumptions in our work nor affects the discussion (interpretation) of the results.

18.
J Biol Phys ; 44(1): 37-50, 2018 03.
Article in English | MEDLINE | ID: mdl-29027614

ABSTRACT

The theoretical basis of neuronal coding, associated with short-term degradation in synaptic transmission, is a matter of debate in the literature. In fact, electrophysiological signals are commonly characterized as inversely proportional to stimulus intensity. Among theoretical descriptions of this phenomenon, models based on 1/f-dependency are employed to investigate the biophysical properties of short-term synaptic depression. In this work, we formulate a model based on a paradigmatic q-differential equation to obtain a generalized formalism useful for investigation of nonextensivity in this specific type of synaptic plasticity. Our analysis reveals nonextensivity in data from electrophysiological recordings and also a statistical crossover in neurotransmission. In particular, statistical transitions provide additional support to the hypothesis of heterogeneous release probability of neurotransmitters. On the other hand, the simple vesicle model agrees with data only at low-frequency stimulations. Thus, the present work presents a method to demonstrate that short-term depression is not only governed by random mechanisms but also by nonextensive behavior. Our findings also conciliate morphological and electrophysiological investigations into a coherent biophysical scenario.


Subject(s)
Models, Neurological , Neurons/cytology , Synaptic Transmission , Time Factors
20.
Genes Brain Behav ; 15(7): 637-46, 2016 09.
Article in English | MEDLINE | ID: mdl-27283753

ABSTRACT

Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.


Subject(s)
Brain/physiopathology , Neurofibromatosis 1/physiopathology , Animals , Behavior, Animal/physiology , Brain/diagnostic imaging , Cognition/physiology , Cognition Disorders/diagnostic imaging , Cognition Disorders/physiopathology , Diffusion Tensor Imaging , Disease Models, Animal , Female , Magnetic Resonance Imaging , Male , Mice , Mice, Inbred C57BL , Neurofibromatosis 1/diagnostic imaging , Phenotype , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Social Behavior , Social Behavior Disorders/physiopathology , Structure-Activity Relationship
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