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1.
Br J Nutr ; : 1-13, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39364656

RESUMEN

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

2.
Cleft Palate Craniofac J ; : 10556656241288192, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39370859

RESUMEN

OBJECTIVE: This bibliometric study seeks to provide a comprehensive overview of the 100 most frequently cited articles in the domain of cleft orthodontics. The analysis will reveal key influential publications, collaborative author networks, and identify prevailing research themes within the field. METHOD: The studies related to Orthodontics in the realm of cleft lip and palate (CLP) were retrieved from the Scopus database on 30th August 2024 using key terms. The results obtained were sorted in descending order of citations and the 100 top-cited articles were hand-filtered. RStudio software version 4.2.0 and Bibliometrix R-package was used for performing scientometrics involving co-citation, co-occurrence, collaboration and co-word analyses, bibliographic coupling and network mapping. RESULTS: A total of n = 3984 articles were retrieved from which top-100 cited articles were filtered. These documents were published during 1950-2019 with peak production in 1997. The United States and the Netherlands were the most prolific countries involved in the given research. The majority of the highly referenced articles pertained to alveolar bone grafting, and treatment outcomes being the second common focus followed by Infant and early orthopedics (Naso-alveolar moulding, Maxillary Protraction) and facial growth during the given period. CONCLUSIONS: Thematic mapping depicted bone grafting, alveoloplasty (infant orthopedics) and maxillofacial development as the more developed core topics than the psychology and self-perception of patients with CLP. Recent research trends have shifted towards three-dimensional assessment methods.

3.
Cureus ; 16(8): e68252, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39350801

RESUMEN

Crown fractures with pulp exposure in mature permanent teeth present a challenging situation that requires immediate attention. Mineral trioxide aggregate (MTA) as a sealing material after pulpotomy has proven to be a reliable treatment in these cases compared to traditional root canal therapy. This case report emphasizes the importance of early diagnosis and careful treatment planning for complicated crown fractures and concussion injuries in a mature permanent incisor of a young child. Total pulpotomy using MTA has proven to be an effective treatment for fractures in young mature incisors with pulp exposure, as evidenced by a one-year follow-up in our case, which showed no discoloration.

4.
Heliyon ; 10(15): e35735, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170533

RESUMEN

Egyptian clover/Berseem (Trifolium alexandrinum L.) is the most popular winter leguminous multi-cut fodder crop widely cultivated in the northwest and central parts of India. Quality seed significantly impacts farm productivity, farmers' profitability, and socioeconomic welfare. Foundation and certified seeds enable high-quality seed production, making breeder seed (BS) the most important link in the seed supply chain. In India, berseem BS indent had increased from 1998 - 99 to 2012-13; afterwards, it followed a constant but decreasing trend. Of the 27 notified cultivars, 24 came into the seed supply chain between 1998-1999 and 2021-2022, indicating high varietal availability to stakeholders. The study examines the potential causes of the national decline in BS indent and production and the differences in these figures over time. The highest BS indent was received for the variety JB-1 (276.1 q), followed by BL-10 (205.1 q), Mescavi (165.6 q) and Wardan (153.7 q) from 1998 - 99 to 2021-22. The varietal replacement rate (VRR) is high, 43.30 %, for the varieties that have reached the age of five or less in the recent three years (2019-20 to 2021-22). Additionally, it has been calculated that if the seed chain operates at 100 % efficiency, the BS generated (48.1q) in 2021-22 can cover an area of almost 0.12 million hectares in 2024-25. The study offers an in-depth overview of berseem BS indent and production, an analysis of the difficulties encountered in BS production, and future directions for expanding variety and producing excess BS in the nation.

5.
J Rheumatol ; 51(8): 781-789, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38879192

RESUMEN

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.


Asunto(s)
Artritis Psoriásica , Aprendizaje Automático , Psoriasis , Teléfono Inteligente , Humanos , Artritis Psoriásica/diagnóstico , Femenino , Masculino , Psoriasis/diagnóstico , Adulto , Persona de Mediana Edad , Prueba de Estudio Conceptual , Aplicaciones Móviles , Reproducibilidad de los Resultados
6.
J Nepal Health Res Counc ; 21(4): 593-598, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38616588

RESUMEN

BACKGROUND: Rheumatic heart disease is a major cause of cardiovascular morbidity and mortality in developing nations and is a leading cause of hospital admission due to cardiac problems in our country. This study will evaluate the association between left atrial size and the occurrence of atrial fibrillation and describe the clinical characteristics along with complications related to Rheumatic Mitral valve disease. METHODS: A retrospective cross-sectional study was conducted at a tertiary care center from January 2018 to December 2019. Reports of 207 patients admitted to medical and/or surgical wards with echocardiographic diagnosis of rheumatic mitral valve disease with or without atrial fibrillation were reviewed. Data were collected, entered, and analyzed using the Statistical Package for the Social Science version 25.0. RESULTS: Among 207 patients, atrial fibrillation was present in 90 (43.5%) patients. Atrial fibrillation was higher in patients with mixed mitral valvular lesions compared to isolated mitral stenosis or mitral regurgitation. Univariate and multivariate analysis revealed left atrial size [aOR=1.067, 95% CI: 1.023 - 1.113, P= 0.002] and age [aOR = 1.073, 95% CI: 1.042 - 1.105, P<0.001] as an independent predictor of atrial fibrillation. CONCLUSIONS: Larger left atrium was an independent predictor of atrial fibrillation. Besides this, atrial fibrillation was associated with increasing age, mixed mitral valvular lesion, and moderately reduced left ventricular ejection fraction, but not associated with gender and mitral stenosis severity. Left atrial clot was significantly higher in patients with atrial fibrillation than in sinus rhythm.


Asunto(s)
Fibrilación Atrial , Estenosis de la Válvula Mitral , Cardiopatía Reumática , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/diagnóstico por imagen , Válvula Mitral/diagnóstico por imagen , Estudios Transversales , Estenosis de la Válvula Mitral/complicaciones , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Nepal , Ecocardiografía
7.
medRxiv ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38585855

RESUMEN

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

8.
RSC Adv ; 14(8): 5037-5044, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38332786

RESUMEN

An effective approach for selective C-N bond formation for synthesising imidazo[1,2-a] pyridine-based heterocycles using porcine pancreatic lipase (PPL) as a biocatalyst has been devised. Under moderate conditions, a series of imidazo[1,2-a]pyridine-based heterocycle derivatives were synthesised with remarkable selectivity in good-to-excellent yields (89-95%). Further, the antimicrobial and antifungal activities of derivatives 3ha, 3ka, 3fa, 3hc, and 3eb were observed, and they were found to be biologically active in antimicrobial susceptibility tests for Gram-positive bacteria (Enterococcus faecalis ATCC 29212 and Staphylococcus auris ATCC 25923), Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and fungal strains (Candida albicans ATCC 90028 and Candida tropicalis ATCC 750).

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124049, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38394884

RESUMEN

Gasoline and diesel are the main petroleum products used for road transportation in India. Due to this reason, adulteration can be done by fraudsters using different miscible substances such as kerosene, turpentine, thinner, ethanol etc. In this work, Fourier transform infrared spectroscopy (FTIR) coupled with principal component analysis (PCA) and partial least square regression (PLSR) were used to investigate adulteration in petroleum products and to design an adulterant profiling. ATR-FTIR has an advantage over other traditional methods as it is less time-consuming and needs no extraction procedure. The samples used for the study were prepared by adding different volume of adulterant (0-20%) to standard diesel and gasoline samples. According to the results obtained from this study, ATR-FTIR spectroscopy proved to be the most comprehensible method for the detection of adulteration in diesel and gasoline fuels. Furthermore, the use of FTIR spectroscopy combined with PCA got best segregation of adulterated samples. The predictive model achieved a root mean square error of prediction of 0.477% and 0.592% for diesel and gasoline respectively.

10.
BMC Med Inform Decis Mak ; 24(1): 57, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378636

RESUMEN

BACKGROUND: The two-way partial AUC has been recently proposed as a way to directly quantify partial area under the ROC curve with simultaneous restrictions on the sensitivity and specificity ranges of diagnostic tests or classifiers. The metric, as originally implemented in the tpAUC R package, is estimated using a nonparametric estimator based on a trimmed Mann-Whitney U-statistic, which becomes computationally expensive in large sample sizes. (Its computational complexity is of order [Formula: see text], where [Formula: see text] and [Formula: see text] represent the number of positive and negative cases, respectively). This is problematic since the statistical methodology for comparing estimates generated from alternative diagnostic tests/classifiers relies on bootstrapping resampling and requires repeated computations of the estimator on a large number of bootstrap samples. METHODS: By leveraging the graphical and probabilistic representations of the AUC, partial AUCs, and two-way partial AUC, we derive a novel estimator for the two-way partial AUC, which can be directly computed from the output of any software able to compute AUC and partial AUCs. We implemented our estimator using the computationally efficient pROC R package, which leverages a nonparametric approach using the trapezoidal rule for the computation of AUC and partial AUC scores. (Its computational complexity is of order [Formula: see text], where [Formula: see text].). We compare the empirical bias and computation time of the proposed estimator against the original estimator provided in the tpAUC package in a series of simulation studies and on two real datasets. RESULTS: Our estimator tended to be less biased than the original estimator based on the trimmed Mann-Whitney U-statistic across all experiments (and showed considerably less bias in the experiments based on small sample sizes). But, most importantly, because the computational complexity of the proposed estimator is of order [Formula: see text], rather than [Formula: see text], it is much faster to compute when sample sizes are large. CONCLUSIONS: The proposed estimator provides an improvement for the computation of two-way partial AUC, and allows the comparison of diagnostic tests/machine learning classifiers in large datasets where repeated computations of the original estimator on bootstrap samples become too expensive to compute.


Asunto(s)
Área Bajo la Curva , Humanos , Simulación por Computador
11.
EMBO Rep ; 25(2): 593-615, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38228788

RESUMEN

Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.


Asunto(s)
Glucemia , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Humanos , Ratones , Embarazo , Glucemia/análisis , Glucemia/metabolismo , Homeostasis , Insulina/metabolismo , Secreción de Insulina , Mamíferos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo
12.
Clin Case Rep ; 11(12): e8314, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38084358

RESUMEN

Key Clinical Message: Immediate thrombolysis in submassive pulmonary embolism on the basis of bedside echocardiography can be a lifesaving decision in areas where computed tomography (CT) pulmonary angiogram is not readily available. Abstract: Bedside echocardiography can be a rapid diagnostic and decision-making tool for immediate thrombolysis in submassive pulmonary embolism with evidence of progressively failing ventricles. We report a case of submassive pulmonary embolism in a 26-year-old male under testosterone replacement therapy, who was successfully thrombolyzed based on bedside echocardiography findings.

13.
Front Plant Sci ; 14: 1259967, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37965034

RESUMEN

Lucerne (Medicago sativa L.) is the second most significant winter leguminous fodder crop after berseem in India. Breeder seed (BS) is the first stage of the seed production chain, as it is the base material for producing foundation and certified seeds. In India, lucerne BS demand has been reduced by 85.58% during the last 24 years (1998-1999 to 2021-2022), declining from 2150 kg to 310 kg. Out of 14 varieties released and notified so far, only nine varieties entered the seed chain since 1998-1999. It shows narrow varietal diversification and, hence, needs robust breeding programs towards enriching genetic variability and varietal development. The present study also highlights the disparity in BS demand and production over the years and puts forth the possible reasons behind the reduction in BS demand and production in the country. Out of the nine varieties, the BS demand of Anand-2 (53.11%) was highest, followed by Type-9 (19.44%) and RL-88 (13.60%). Varietal replacement rate (VRR) was found to be moderate, i.e., 23.67% for the varieties having <5 years old age in the last 3 years (2019-2020 to 2021-2022). It has also been estimated that BS produced (233 kg) during 2021-2022 can cover the approximate area of 6,300 ha at farmers' fields in 2024-2025 if the seed chain functions 100%, effectively. The present study provides a holistic overview of lucerne BS demand and production, challenges in BS production, and the way forward to develop more varieties and surplus BS production in the country.

14.
Cureus ; 15(10): e46479, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37927637

RESUMEN

Several morphological abnormalities may occur during tooth development and may be a predisposing factor for periodontal destruction. Palatogingival groove (PGG) is a developmental deformity that may cause localized periodontitis and endodontic complexities. The groove usually originates as a root indentation in the central fossa of the palatal root of maxillary lateral incisors. Cone beam computed tomography (CBCT) is an excellent radiographic imaging technique capable of identifying PGGs and provides details about the exact site, extent, and depth characteristics of this deformity. Early diagnosis and management of PGGs are of utmost importance, particularly due to their diagnostic intricacies that can pose both clinical and therapeutic challenges. This article aims to report a rare case of palatogingival groove associated with an on-and-off discharge from the maxillary left lateral incisor tooth (#22). Nonsurgical endodontic treatment was carried out with #22, and the palatogingival groove was sealed with composite restoration after a deep curettage. Excellent radiographic healing was observed after a six-month follow-up.

15.
Ann Med Surg (Lond) ; 85(10): 5105-5109, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37811028

RESUMEN

Introduction and importance: Aluminum phosphide (ALP) is a commonly used suicidal agent in an agrarian country like Nepal. The unmasking of the Brugada pattern in the electrocardiogram (ECG) associated with ALP poisoning is a rare phenomenon, and studies pertaining to it are scarce in the medical literature. Case presentation: An 18-year-old female presented to the emergency department with multiple episodes of vomiting, headache, blurring of vision, and abdominal pain after 4 h of consumption of ALP with suicidal intent. A 12-lead ECG revealed a coved ST-segment elevation and T-wave inversion in leads V1-V3 with right bundle branch block suggestive of a type 1 Brugada pattern. Her past medical and family history was not significant. The patient made an uneventful recovery with the required supportive treatments. Clinical discussion: Cardiac arrhythmias are the major cause of death in ALP poisoning. Unmasking of the Brugada ECG pattern is a rare but potentially fatal complication implicated in various pharmacological toxicities, including tricyclic antidepressants, cocaine, procainamide, disopyramide, flecainide, and rarely with ALP. Conclusions: ALP poisoning can unmask the Brugada ECG pattern, which can lead to ventricular fibrillation and/or sudden cardiac death.

16.
bioRxiv ; 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37645714

RESUMEN

Many physiological functions regulated by osteocalcin are affected in adult offspring of mothers experiencing an unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin functions during pregnancy may be a broader determinant of organismal homeostasis in adult mammals than previously thought. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin -deficient, newborn, and adult mice of various genotypes and origin, and that were maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are themselves Osteocalcin -deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that through their synergistic regulation of multiple physiological functions, osteocalcin ofmaternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

17.
J Alzheimers Dis ; 95(3): 995-1011, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37638446

RESUMEN

BACKGROUND: Cognitive decline is a common consequence of COVID-19, and studies suggest a link between COVID-19 and Alzheimer's disease (AD). However, the molecular mechanisms underlying this association remain unclear. OBJECTIVE: To understand the potential molecular mechanisms underlying the association between COVID-19 and AD development, and identify the potential genetic targets for pharmaceutical approaches to reduce the risk or delay the development of COVID-19-related neurological pathologies. METHODS: We analyzed transcriptome datasets of 638 brain samples using a novel Robust Rank Aggregation method, followed by functional enrichment, protein-protein, hub genes, gene-miRNA, and gene-transcription factor (TF) interaction analyses to identify molecular markers altered in AD and COVID-19 infected brains. RESULTS: Our analyses of frontal cortex from COVID-19 and AD patients identified commonly altered genes, miRNAs and TFs. Functional enrichment and hub gene analysis of these molecular changes revealed commonly altered pathways, including downregulation of the cyclic adenosine monophosphate (cAMP) signaling and taurine and hypotaurine metabolism, alongside upregulation of neuroinflammatory pathways. Furthermore, gene-miRNA and gene-TF network analyses provided potential up- and downstream regulators of identified pathways. CONCLUSION: We found that downregulation of cAMP signaling pathway, taurine metabolisms, and upregulation of neuroinflammatory related pathways are commonly altered in AD and COVID-19 pathogenesis, and may make COVID-19 patients more susceptible to cognitive decline and AD. We also identified genetic targets, regulating these pathways that can be targeted pharmaceutically to reduce the risk or delay the development of COVID-19-related neurological pathologies and AD.


Asunto(s)
Enfermedad de Alzheimer , COVID-19 , MicroARNs , Humanos , Enfermedad de Alzheimer/patología , Perfilación de la Expresión Génica , COVID-19/genética , MicroARNs/genética , Factores de Transcripción/genética , Desarrollo de Medicamentos , Taurina
18.
Theriogenology ; 211: 125-133, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37619525

RESUMEN

Bone Morphogenetic Proteins play a significant role in ovarian physiology and contribute to the reproductive fitness of mammals. The BMPR-1B/FecB mutation, a loss of function mutation increases litter size by 1-2 with each number of mutated alleles in sheep. Considering demand-supply gap of the meat industry, and low replacement rate of indigenous caprine species, the conservative BMPR-1B locus can be explored, and FecB mutated goats can be produced. The experiment one produced CRISPR/Cas mediated KO transferable caprine embryos, and experiment two generated caprine embryos with desired FecB mutation using Easi-CRISPR strategy. In the KO experiment, Cas9 and BMPR-1B guide RNA (100:100ng/ul) were electroporated into single stage caprine zygotes at 750V, 10 ms and 1pulse using Neon transfection system. In the second experiment, phosphorothioate (PS) modified single-stranded oligodeoxynucleotide (ssODN) was used as an HDR template along with CRISPR components (100:100ng/ul, ssODN 100ng/ul). The precise time and method of electroporation, RNP format of CRISPR components and PS modified asymmetric ssODN were the factors that affected the production of mosaicism free BMPR-1B edited caprine embryos. The editing efficiency of KO and KI experiments was 68.52 and 63.16% respectively, and successful production of goats with higher mean ovulation rate can be realized with addition of embryo transfer technology to these experiments.


Asunto(s)
Sistemas CRISPR-Cas , Cabras , Femenino , Animales , Ovinos , Cabras/genética , Mutación , Alelos , Terapia de Electroporación/veterinaria
19.
bioRxiv ; 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37398415

RESUMEN

Cognitive decline has been reported as a common consequence of COVID-19, and studies have suggested a link between COVID-19 infection and Alzheimer's disease (AD). However, the molecular mechanisms underlying this association remain unclear. To shed light on this link, we conducted an integrated genomic analysis using a novel Robust Rank Aggregation method to identify common transcriptional signatures of the frontal cortex, a critical area for cognitive function, between individuals with AD and COVID-19. We then performed various analyses, including the KEGG pathway, GO ontology, protein-protein interaction, hub gene, gene-miRNA, and gene-transcription factor interaction analyses to identify molecular components of biological pathways that are associated with AD in the brain also show similar changes in severe COVID-19. Our findings revealed the molecular mechanisms underpinning the association between COVID-19 infection and AD development and identified several genes, miRNAs, and TFs that may be targeted for therapeutic purposes. However, further research is needed to investigate the diagnostic and therapeutic applications of these findings.

20.
Chaos ; 33(6)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37327496

RESUMEN

Machine learning has proven exceptionally competent in numerous applications of studying dynamical systems. In this article, we demonstrate the effectiveness of reservoir computing, a famous machine learning architecture, in learning a high-dimensional spatiotemporal pattern. We employ an echo-state network to predict the phase ordering dynamics of 2D binary systems-Ising magnet and binary alloys. Importantly, we emphasize that a single reservoir can be competent enough to process the information from a large number of state variables involved in the specific task at minimal computational training cost. Two significant equations of phase ordering kinetics, the time-dependent Ginzburg-Landau and Cahn-Hilliard-Cook equations, are used to depict the result of numerical simulations. Consideration of systems with both conserved and non-conserved order parameters portrays the scalability of our employed scheme.


Asunto(s)
Aprendizaje Automático , Física , Cinética
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