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The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons. These mice showed disturbed diurnal rhythms of GABAA receptor-mediated synaptic transmission in SCN neurons and marked lengthening of the activity time in circadian behavioral rhythms due to the extended interval between morning and evening locomotor activities. Synchrony of molecular circadian oscillations among SCN neurons did not significantly change, whereas the phase relationships between SCN molecular clocks and circadian morning/evening locomotor activities were altered significantly, as revealed by PER2::LUC imaging of SCN explants and in vivo recording of intracellular Ca2+ in SCN AVP neurons. In contrast, daily neuronal activity in SCN neurons in vivo clearly showed a bimodal pattern that correlated with dissociated morning/evening locomotor activities. Therefore, GABAergic transmission from AVP neurons regulates the timing of SCN neuronal firing to temporally restrict circadian behavior to appropriate time windows in SCN molecular clocks.
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Relógios Circadianos , Ritmo Circadiano , Neurônios/metabolismo , Núcleo Supraquiasmático/metabolismo , Vasopressinas/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Comportamento Animal , Cálcio/metabolismo , Relógios Circadianos/genética , Ritmo Circadiano/genética , Regulação da Expressão Gênica , Locomoção , Camundongos , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Fatores de Tempo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/deficiência , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismoRESUMO
OBJECTIVES: Characterisation of resistance phenotype and genotype is crucial to understanding the burden and transmission of antimicrobial resistance (AMR). This study aims to determine the spectrum of AMR and associated genes encoding aminoglycoside, macrolide and ß-lactam classes of antimicrobials in bacteria isolated from hospitalised patients in Bangladesh. METHODS: 430 bacterial isolates from patients with respiratory, intestinal, wound infections and typhoid fever, presenting to clinical care from 2015 to 2019, were examined. They included Escherichia coli (n = 85); Staphylococcus aureus (n = 84); Salmonella typhi (n = 82); Klebsiella pneumoniae (n = 42); Streptococcus pneumoniae (n = 36); coagulase-negative staphylococci (n = 28); Enterococcus faecalis (n = 27); Pseudomonas aeruginosa (n = 26); and Acinetobacter baumannii (n = 20). Reconfirmation of these clinical isolates and antimicrobial susceptibility tests was performed. PCR amplification using resistance gene-specific primers was done, and the amplified products were confirmed by Sanger sequencing. RESULTS: 53% of isolates were multidrug-resistant (MDR), including 97% of Escherichia coli. There was a year-wise gradual increase in MDR isolates from 2015 to 2018, and there was an almost twofold increase in the number of MDR strains isolated in 2019 (P = 0.00058). Among the 5 extended-spectrum ß-lactamases investigated, CTX-M-1 was the most prevalent (63%) followed by NDM-1 (22%); Escherichia coli was the major reservoir of these genes. The ermB (55%) and aac(6')-Ib (35%) genes were the most frequently detected macrolide and aminoglycoside resistance genes, respectively. CONCLUSION: MDR pathogens are highly prevalent in hospital settings of Bangladesh.
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Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana Múltipla/fisiologia , Genótipo , Fenótipo , Acinetobacter baumannii/isolamento & purificação , Bangladesh , Enterococcus faecalis/isolamento & purificação , Escherichia coli/isolamento & purificação , Humanos , Pacientes Internados , Klebsiella pneumoniae/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Salmonella typhi/isolamento & purificação , Staphylococcus aureus/isolamento & purificaçãoRESUMO
BACKGROUND: Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous males and homozygous females, heterozygous females could also manifest hemolytic crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative stress induced by certain foods such as fava beans, drugs or infections. Although hemizygous males and homozygous females are easily detected by conventional G6PD enzyme assay method, the heterozygous state could be missed by the conventional methods as the mosaic population of both normal and deficient RBCs circulates in the blood. Thus the present study aimed to apply high resolution melting (HRM) curve analysis approach to see whether HRM could be used as a supplemental approach to increase the chance of detection of G6PD heterozygosity. RESULTS: Sixty-three clinically suspected females were evaluated for G6PD status using both enzyme assay and HRM analysis. Four out of sixty-three participants came out as G6PD deficient by the enzyme assay method, whereas HRM approach could identify nine participants with G6PD variants, one homozygous and eight heterozygous. Although only three out of eight heterozygous samples had G6PD enzyme deficiency, the HRM-based heterozygous G6PD variants detection for the rest of the samples with normal G6PD enzyme activities could have significance because their newborns might fall victim to serious consequences under certain oxidative stress. CONCLUSIONS: In addition to the G6PD enzyme assay, HRM curve analysis could be useful as a supplemental approach for detection of G6PD heterozygosity.
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Análise Mutacional de DNA/métodos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Heterozigoto , Mutação , Adolescente , Criança , Pré-Escolar , Feminino , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Recém-Nascido , Desnaturação de Ácido NucleicoRESUMO
BACKGROUND: Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. RESULTS: Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. CONCLUSIONS: Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and electrophortic indices in order to avoid false positive and false negative results.
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Triagem de Portadores Genéticos/métodos , Hibridização de Ácido Nucleico/métodos , Globinas beta/genética , Talassemia beta/diagnóstico , Adolescente , Bangladesh , Criança , Pré-Escolar , Triagem de Portadores Genéticos/economia , Hemoglobina E/genética , Humanos , Lactente , Mutação , Talassemia beta/genéticaRESUMO
An experimental system for early screening of a breast tumor is presented in this article. The proposed microwave imaging (MI) system consists of a moveable array of nine improved negative-index metamaterial (MTM)-loaded ultrawideband (UWB) antenna sensor with incorporation of a corresponding SRR (split-ring resonator) and CLS (capacitively loaded strip) structure, in a circular array, the stepper motor-based array-mounting stand, the adjustable phantom hanging platform, an RF switching system to control the receivers, and a personal computer-based signal processing and image reconstruction unit using MATLAB. The improved antenna comprises of four-unit cells along one axis, where an individual unit cell integrates a balancing SRR and CLS pair, which makes the antenna radiation omnidirectional over the operating frequencies. The electrical dimensions of this proposed antenna are 0.28λ × 0.20λ × 0.016λ, measured at the lowest operating frequency of 2.97 GHz as the operating bandwidth of this is in between 2.97â»15 GHz (134.82% bandwidth), with stable directional radiation pattern. SP8T 8 port switch is used to enable the eight receiver antennas to sequentially send a 3â»8.0 GHz microwave signal to capture the backscattered signal by MATLAB software. A low-cost realistic homogeneous breast phantom with tumor material is developed and measured to test the capability of the imaging system to detect the breast tumors. A post-processing delay-multiply-and-sum (DMAS) algorithm is used to process the recorded backscatter signal to get an image of the breast phantom, and to accurately identify the existence and located area of multiple breast tumor tissues.
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Neoplasias da Mama/diagnóstico por imagem , Imagens de Fantasmas , Algoritmos , Desenho de Equipamento , Humanos , Micro-OndasRESUMO
Microwave breast imaging has been reported as having the most potential to become an alternative or additional tool to the existing X-ray mammography technique for detecting breast tumors. Microwave antenna sensor performance plays a significant role in microwave imaging system applications because the image quality is mostly affected by the microwave antenna sensor array properties like the number of antenna sensors in the array and the size of the antenna sensors. In this paper, a new system for successful early detection of a breast tumor using a balanced slotted antipodal Vivaldi Antenna (BSAVA) sensor is presented. The designed antenna sensor has an overall dimension of 0.401λ × 0.401λ × 0.016λ at the first resonant frequency and operates between 3.01 to 11 GHz under 10 dB. The radiating fins are modified by etching three slots on both fins which increases the operating bandwidth, directionality of radiation pattern, gain and efficiency. The antenna sensor performance of both the frequency domain and time domain scenarios and high-fidelity factor with NFD is also investigated. The antenna sensor can send and receive short electromagnetic pulses in the near field with low loss, little distortion and highly directionality. A realistic homogenous breast phantom is fabricated, and a breast phantom measurement system is developed where a two antennas sensor is placed on the breast model rotated by a mechanical scanner. The tumor response was investigated by analyzing the backscattering signals and successful image construction proves that the proposed microwave antenna sensor can be a suitable candidate for a high-resolution microwave breast imaging system.
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BACKGROUND: Hexokinase, a key enzyme in glycolysis, has isoforms like HK-1, HK-2, HK-3, and Glucokinase. Unpublished exome sequencing data showed that two novel polymorphisms in HK-1 rs201626997 (G/T) and HK-3 rs143604141 (G/A) exist in the Bangladeshi population. We investigated the possible relationship of these SNPs with T2DM. MATERIALS AND METHODS: Peripheral blood samples from the study participants were used to isolate their genomic DNA. An allele-specific PCR was standardized that can discriminate between the wild-type and mutant-type alleles of HK-1 (rs201626997) and HK-3 (rs143604141) polymorphisms. The data was analyzed by SPSS for statistics. RESULTS: We performed allele-specific PCR for 249 diabetic patients and 195 control samples. For HK-1 (rs201626997), 24 (5.4%) have a mutant allele, and for HK-3 (rs143604141), 25 (5.6%) are mutant. There is no significant relationship between the individuals' disease condition and the HK-1 polymorphism (P value 0.537). But the GA genotype of the HK-3 rs143604141 pertains to an increased risk of diabetes (P value 0.039). HK-3 rs143604141 polymorphism has a moderate correlation (P value 0.078, OR, 3.11, 95% CI, 0.88-10.94) with a family diabetic history. Both polymorphisms showed no significant correlation with gender or BMI. However, hexokinase-1 polymorphism significantly related with diastolic blood pressure (P value 0.048). CONCLUSION: This study will help us to easily detect the polymorphisms of HK-1 (rs201626997) and HK-3 (rs143604141) in different populations of the world. Further studies with a greater number of participants and more physiological information are required to better understand the underlying genetic causes of T2DM susceptibility in Bangladesh.
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Diabetes Mellitus Tipo 2 , Predisposição Genética para Doença , Hexoquinase , Polimorfismo de Nucleotídeo Único , Humanos , Hexoquinase/genética , Diabetes Mellitus Tipo 2/genética , Bangladesh/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Estudos de Associação Genética , Frequência do Gene , Alelos , IdosoRESUMO
Numerous studies have identified dopamine signaling in the hippocampus as necessary for certain types of learning and memory. Since dopamine in the striatum is strongly tied to rewards, dopamine in the hippocampus is thought to reinforce reward learning. Despite the critical influence of dopamine on hippocampal function, little is known about dopamine release in the hippocampus or the specific ways dopamine can influence hippocampal function. Based on the functional complexity of hippocampal circuitry, we hypothesized the existence of multiple dopamine signaling domains. Using optical dopamine sensors, two-photon imaging, and head-fixed behaviors, we identified two functionally and spatially distinct dopamine domains in the hippocampus. The "superficial" domain (cell somata and apical dendrites) showed reward-related dopamine transients early in Pavlovian conditioning but were replaced by "deep" domain transients (basal dendritic layer) with experience. These two domains also play distinct roles in a hippocampal-dependent, goal-directed virtual reality task where mice use exploratory licks to discover the location of a hidden reward zone. Here, positive dopamine ramps appeared in the superficial domain as mice approached the reward zone, similar to those seen in the striatum. At the same time, the deep domain showed strong reward-related transients. These results reveal small-scale, anatomically segregated, dopamine domains in the hippocampus. Furthermore dopamine domain activity had temporal-specificity for different phases of behavior. Finally, the subcellular scale of dopamine domains suggests specialized postsynaptic pathways for processing and integrating functionally distinct dopaminergic influences.
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Dengue fever (DF) is an endemic disease that has become a public health concern around the globe. The NS3 protease-helicase enzyme is an important target for the development of antiviral drugs against DENV (dengue virus) due to its impact on viral replication. Inhibition of the activity of the NS3 protease-helicase enzyme complex significantly inhibits the infection associated with DENV. Unfortunately, there are no scientifically approved antiviral drugs for its prevention. However, this study has been developed to find natural bioactive molecules that can block the activity of the NS3 protease-helicase enzyme complex associated with DENV infection through molecular docking, MM-GBSA (molecular mechanics-generalized born surface area), and molecular dynamics (MD) simulations. Three hundred forty-two (342) compounds selected from twenty traditional medicinal plants were retrieved and screened against the NS3 protease-helicase protein by molecular docking and MM-GBSA studies, where the top six phytochemicals have been identified based on binding affinities. The six compounds were then subjected to pharmacokinetics and toxicity analysis, and we conducted molecular dynamics simulations on three protein-ligand complexes to validate their stability. Through computational analysis, this study revealed the potential of the two selected natural bioactive inhibitors (CID-440015 and CID-7424) as novel anti-dengue agents.
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This review paper exhibits the underexplored realm of heavy metal contamination and associated risks in sea cucumbers (SCs), which hold significant importance in traditional Asian marine diets and are globally harvested for the Asian market. The assessment focuses on heavy metals (HMs) presence in various SC species, revealing a global trend in HMs concentrations across anatomical parts: Fe > Zn > As > Cu > Hg > Pb > Mn > Cr > Ni > Cd. Specific species, such as Eupentacta fraudatrix, Holothuria mammata, Holothuria polii, Holothuria tubulosa, and Holothuria atra, exhibit heightened arsenic levels, while Stichopus herrmanni raises concerns with mercury levels, notably reaching 3.75 mg/kg in some instances, posing potential risks, particularly for children. The study sheds light on anthropogenic activities such as cultivation, fishing, and shipping, releasing HMs into marine ecosystems and thereby threatening ocean and coastal environments due to the accumulation and toxicity of these elements. In response to these findings, the paper suggests SCs as promising bioindicator species for assessing metal pollution in marine environments. It underscores the adverse effects of human actions on sediment composition and advocates for ongoing monitoring efforts both at sea and along coastlines.
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Metais Pesados , Pepinos-do-Mar , Poluentes Químicos da Água , Animais , Criança , Humanos , Biomarcadores Ambientais , Ecossistema , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Metais Pesados/análise , Sedimentos Geológicos , Medição de RiscoRESUMO
TPO (Thyroid Peroxidase) is known to be one of the major genes involved in congenital hypothyroid patients with thyroid dyshormonogenesis. The present study aims to validate high-resolution melting (HRM) curve analysis as a substitute method for Sanger sequencing, focusing on the frequently observed non-synonymous mutations c.1117G>T, c.1193G>C, and c.2173A>C in the TPO gene in patients from Bangladesh. We enrolled 36 confirmed cases of congenital hypothyroid patients with dyshormonogenesis to establish the HRM method. Blood specimens were collected, and DNA was extracted followed by PCR and Sanger sequencing. Among the 36 specimens, 20 were pre-sequenced, and variants were characterized through Sanger sequencing. Following pre-sequencing, the 20 pre-sequenced specimens underwent real-time PCR-HRM curve analysis to determine the proper HRM condition for separating the three variations from the wild-type state into heterozygous and homozygous states. Furthermore, 16 unknown specimens were subjected to HRM analysis to validate the method. This method demonstrated a sensitivity and specificity of 100 percent in accurately discerning wild-type alleles from both homozygous and heterozygous states of c.1117G>T (23/36; 63.8%), c.1193G>C (30/36; 83.3%), and c.2173A>C (23/36; 63.8%) variants frequently encountered among 36 Bangladeshi patients. The HRM data was found to be similar to the sequencing result, thus confirming the validity of the HRM approach for TPO gene variant detection. In conclusion, HRM-based molecular technique targeting variants c.1117G>T, c.1193G>C, and c.2173A>C could be used as a high throughput, rapid, reliable, and cost-effective screening approach for the detection of all common mutations in TPO gene in Bangladeshi patients with dyshormonogenesis.
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Hipotireoidismo Congênito , Humanos , Bangladesh , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Mutação , DNA , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Brain hemorrhage, specifically intraventricular hemorrhage (IVH), is considered one of the primary and leading causes of cerebral anomalies in neonates. Several imaging modalities including the most popular, cranial ultrasound, are not capable of detecting early stage IVHs. Photoacoustic imaging (PAI) exhibited great potential for detecting cerebral hemorrhage in studies limited to small animal models, but these models are not comparable to neonatal brain morphology. However, hemorrhage detection in large animal models using PAI is rare due to the complexity and cost of inducing hemorrhage in vivo. Moreover, in vitro studies are unable to represent the physiology and environment of the hemorrhagic lesion. Here, we proposed a pseudo hemorrhage implementation method in the sheep brain that allows us to mimic different hemorrhagic lesions ex vivo without compromising the complexity of cerebral imaging. This approach enables a true evaluation of PAI performance for detecting hemorrhages and can be utilized as a reference to optimize the PAI system for in vivo imaging.
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Encéfalo , Hemorragia Cerebral , Imagens de Fantasmas , Técnicas Fotoacústicas , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Técnicas Fotoacústicas/métodos , Humanos , Recém-Nascido , Animais , Ovinos , Modelos Animais de DoençasRESUMO
The disorder of thyroid gland development or thyroid dysgenesis accounts for 80-85% of congenital hypothyroidism (CH) cases. Mutations in the TSHR gene are mostly associated with thyroid dysgenesis, and prevent or disrupt normal development of the gland. There is limited data available on the genetic spectrum of congenital hypothyroid children in Bangladesh. Thus, an understanding of the molecular aetiology of thyroid dysgenesis is a prerequisite. The aim of the study was to investigate the effect of mutations in the TSHR gene on the small molecule thyrogenic drug-binding site of the protein. We identified two nonsynonymous mutations (p.Ser508Leu, p.Glu727Asp) in the exon 10 of the TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, the TSHR368-764 protein was modeled by the I-TASSER server for wild-type and mutant structures. The model proteins were targeted by thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants was explored by molecular docking and molecular dynamics simulations. The binding affinity of wild-type protein was much higher than the mutant cases for both of the drug ligands (MS437 and MS438). Molecular dynamics simulates the dynamic behavior of wild-type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 showed stable conformations in biological environments. Finally, Principle Component Analysis revealed structural and energy profile discrepancies. TSHR368-764MT1 exhibited much more variations than TSHR368-764WT and TSHR368-764MT2, emphasizing a more damaging pattern in TSHR368-764MT1. This genetic study might be helpful to explore the mutational impact on drug binding sites of TSHR protein which is important for future drug design and selection for the treatment of congenital hypothyroid children with dysgenesis.
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Hipotireoidismo Congênito , Disgenesia da Tireoide , Criança , Humanos , Bangladesh , Hipotireoidismo Congênito/genética , Simulação de Acoplamento Molecular , Mutação , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismoRESUMO
Background: The use of silver is rapidly rising in wound care and silver-containing dressings are widely used along with other antibiotics, particularly ß-lactams. Consequently, concerns are being raised regarding the emergence of silver-resistance and cross-resistance to ß-lactams. Therefore, this study aimed to determine the phenotypic and genotypic profiles of silver-resistance and extended-spectrum ß-lactamases in isolates from chronic wounds. Methods: 317 wound swab specimens were collected from tertiary hospitals of Dhaka city and analysed for the microbial identification. The antibiotic resistance/susceptibility profiles were determined and phenotypes of silver resistant isolates were examined. The presence of silver-resistance (sil) genes (silE, silP, and silS) and extended-spectrum ß-lactamases (ESBL) (CTX-M-1, NDM-1, KPC, OXA-48, and VIM-1) were explored in isolated microorganisms. Results: A total of 501 strains were isolated with Staphylococcus aureus (24%) as the predominant organism. In 29% of the samples, polymicrobial infections were observed. A large proportion of Enterobacterales (59%) was resistant to carbapenems and a significantly high multiple antibiotic-resistance indexes (>0.2) were seen for 53% of organisms (P < 0.001). According to molecular analysis, the most prevalent types of ESBL and sil gene were CTX-M-1 (47%) and silE (42%), respectively. Furthermore, phenotypic silver-nitrate susceptibility testing showed significant minimum-inhibitory-concentration patterns between sil-negative and sil-positive isolates. We further observed co-occurrence of silver-resistance determinants and ESBLs (65%). Conclusions: Notably, this is the first-time detection of silver-resistance along with its co-detection with ESBLs in Bangladesh. This research highlights the need for selecting appropriate treatment strategies and developing new alternative therapies to minimize microbial infection in wounds.
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Intraventricular (IVH) and periventricular (PVH) hemorrhages in preterm neonates are common because the periventricular blood vessels are still developing up to 36 weeks and are fragile. Currently, transfontanelle ultrasound (US) imaging is utilized for screening for IVH and PVH, largely through the anterior fontanelle. However for mild hemorrhages, inconclusive diagnoses are common, leading to failure to detect IVH/PVH or, when other clinical symptoms are present, use of second stage neuroimaging modalities requiring transport of vulnerable patients. Yet even mild IVH/PVH increases the risk of moderate-severe neurodevelopmental impairment. Here, we demonstrate the capability of transfontanelle photoacoustic imaging (TFPAI) to detect IVH and PVH in-vivo in a large animal model. TFPAI was able to detect IVH/PVH as small as 0.3 mL in volume in the brain (p < 0.05). By contrast, US was able to detect hemorrhages as small as 0.5 mL. These preliminary results suggest TFPAI could be translated into a portable bedside imaging probe for improved diagnosis of clinically relevant brain hemorrhages in neonates.
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Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of -9.2, -9.0, and -8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (-7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles' root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein-ligand complexes' better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.
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Self-grooming plays an essential role in hygiene maintenance, thermoregulation, and stress response. However, the neural populations involved in self-grooming remain largely unknown. The paraventricular hypothalamic nucleus (PVH) has been implicated in the regulation of self-grooming. Arginine vasopressin-producing neurons are among the major neuronal populations in the PVH (PVHAVP), which play important roles in water homeostasis, blood pressure regulation, feeding, and stress response. Here, we report the critical role of PVHAVP neurons in the induction of self-grooming. Optogenetic activation of PVHAVP neurons immediately induced self-grooming in freely moving mice. Chemogenetic activation of these neurons also increased time spent self-grooming. In contrast, their chemogenetic inhibition significantly reduced naturally occurring self-grooming, suggesting that PVHAVP-induced grooming has physiological relevance. Notably, optogenetic activation of PVHAVP neurons triggered self-grooming over other adaptive behaviors, such as voracious feeding induced by fasting and social interaction with female mice. Thus, our study proposes the novel role of PVHAVP neurons in regulating self-grooming behavior and, consequently, hygiene maintenance and stress response. Furthermore, uncontrolled activation of these neurons may be potentially relevant to diseases characterized by compulsive behaviors and impaired social interaction, such as autism, obsessive-compulsive disorder, and anorexia nervosa.
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Arginina Vasopressina , Núcleo Hipotalâmico Paraventricular , Animais , Arginina Vasopressina/genética , Arginina Vasopressina/metabolismo , Feminino , Asseio Animal , Camundongos , Neurônios/metabolismo , Optogenética , Núcleo Hipotalâmico Paraventricular/metabolismoRESUMO
Transfontanelle ultrasound imaging (TFUI) is the conventional approach for diagnosing brain injury in neonates. Despite being the first stage imaging modality, TFUI lacks accuracy in determining the injury at an early stage due to degraded sensitivity and specificity. Therefore, a modality like photoacoustic imaging that combines the advantages of both acoustic and optical imaging can overcome the existing TFUI limitations. Even though a variety of transducers have been used in TFUI, it is essential to identify the transducer specification that is optimal for transfontanelle imaging using the photoacoustic technique. In this study, we evaluated the performance of 6 commercially available ultrasound transducer arrays to identify the optimal characteristics for transfontanelle photoacoustic imaging. We focused on commercially available linear and phased array transducer probes with center frequencies ranging from 2.5MHz to 8.5MHz which covers the entire spectrum of the transducer arrays used for brain imaging. The probes were tested on both in vitro and ex vivo brain tissue, and their performance in terms of transducer resolution, size, penetration depth, sensitivity, signal to noise ratio, signal amplification and reconstructed image quality were evaluated. The analysis of selected transducers in these areas allowed us to determine the optimal transducer for transfontanelle imaging, based on vasculature depth and blood density in tissue using ex vivo sheep brain. The outcome of this evaluation identified the two most suitable ultrasound transducer probes for transfontanelle photoacoustic imaging.
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Nickel particles alone can oxidize hydrogen peroxide but confronts extreme stability problem which imparts a barrier to act as sensor. The porous Nafion bed on glassy carbon electrode (GCE) surface provides the sureness of incorporating of Ni particles which was further exploited as an electrochemical sensor for H2O2 detection through oxidative degradation process. The simple electrochemical incorporation of Ni particles along the pores of Nafion improves the stability of the sensor significantly. The oxidative pathway of hydrogen peroxide on GCE/Nafion/Ni was probed by analyzing mass transfer dependent linear sweep voltammograms both in static and rotating modes along with chronoamperometry. An electron transfer step determines the overall reaction rate with k°= 2.72 × 10-4 cm s-1, which is supported by the values of transfer coefficient (ß) in between (0.68-0.75). Sensing performance was evaluated by recording differential pulse voltammograms (DPVs) with the linear detection limit (LOD) of 1.8 µM and linear dynamic range (LDR) of 5-500 µM. Real samples from industrial sources were successfully quantified with excellent reproducibility mark GCE/Nafion/Ni electrode as an applicable sensor.
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Carbono , Peróxido de Hidrogênio , Técnicas Eletroquímicas , Eletrodos , Polímeros de Fluorcarboneto , Reprodutibilidade dos TestesRESUMO
The capability of photoacoustic (PA) imaging to measure oxygen saturation through a fontanelle has been demonstrated in large animals in-vivo. We called this method, transfontanelle photoacoustic imaging (TFPAI). A surgically induced 2.5 cm diameter cranial window was created in an adult sheep skull to model the human anterior fontanelle. The performance of the TFPAI has been evaluated by comparing the PA-based predicted results against the gold standard of blood gas analyzer measurements.