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2.
bioRxiv ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39091801

RESUMEN

The RNA genome of measles virus is encapsidated by the nucleoprotein within a helical nucleocapsid that serves as template for both transcription and replication. The intrinsically disordered domain of the nucleoprotein (NTAIL), partly protruding outward from the nucleocapsid, is essential for binding the polymerase complex responsible for viral transcription and replication. As for many IDPs, binding of NTAIL occurs through a short molecular recognition element (MoRE) that folds upon binding, with the majority of NTAIL remaining disordered. Though NTAIL regions far from the MoRE influence the binding affinity, interactions between them and the MoRE have not been investigated in depth. Using an integrated approach, relying on photo-induced electron transfer (PET) experiments between tryptophan and cysteine pairs placed at different positions in the protein under varying salt and pH conditions, combined with simulations and analytical models, we identified transient interactions between two disordered regions distant in sequence, which dominate NTAIL dynamics, and regulate the conformational preferences of both the MoRE and the entire NTAIL domain. Co-evolutionary analysis corroborates our findings, and suggests an important functional role for the same intramolecular interactions. We propose mechanisms by which these non-local interactions may regulate binding to the phosphoprotein, polymerase recruitment, and ultimately viral transcription and replication. Our findings may be extended to other IDPs, where non-local intra-protein interactions affect the conformational preferences of intermolecular binding sites.

3.
Microbiol Spectr ; : e0110324, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189757

RESUMEN

Survival factor 1 (Svf1) protein has been described in some ascomycetous fungi where it was found to be contributing to several essential physiological processes, such as response to osmotic, oxidative and cold stresses, sphingolipid biosynthesis, morphogenesis, sporulation, antifungal resistance, and pathogenicity. It was also suggested that it can be a novel central regulator affecting the expression of various genes. In the present study, function of this protein and the encoding genes is described for the first time in a fungus (i.e., in Mucor lusitanicus) belonging to the order Mucorales. M. lusitanicus has two putative svf1 genes named svf1a and svf1b. Expression of both genes was proven. Although the expression of svf1a was affected by several environmental stresses and knocking out the gene affected adaptation to low temperatures and the sporulation ability, the main survival factor functions, such as participation in the maintenance of the viability, the response to oxidative and cold stresses, and the sphingolipid biosynthesis, could be associated with Svf1b, suggesting a central regulatory role to this protein. Interestingly, knockout of both genes affected the pathogenicity of the fungus in a Drosophila model. IMPORTANCE: Mucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.

4.
Physiol Plant ; 176(4): e14504, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39191700

RESUMEN

Plant infections caused by fungi lead to significant crop losses worldwide every year. This study aims to better understand the plant defence mechanisms regulated by red light, in particular, the effects of red light at night when most phytopathogens are highly infectious. Our results showed that superoxide production significantly increased immediately after red light exposure and, together with hydrogen peroxide levels, was highest at dawn after 30 min of nocturnal red-light treatment. In parallel, red-light-induced expression and increased the activities of several antioxidant enzymes. The nocturnal red light did not affect salicylic acid but increased jasmonic acid levels immediately after illumination, whereas abscisic acid levels increased 3 h after nocturnal red-light exposure at dawn. Based on the RNAseq data, red light immediately increased the transcription of several chloroplastic chlorophyll a-b binding protein and circadian rhythm-related genes, such as Constans 1, CONSTANS interacting protein 1 and zinc finger protein CONSTANS-LIKE 10. In addition, the levels of several transcription factors were also increased after red light exposure, such as the DOF zinc finger protein and a MYB transcription factor involved in the regulation of circadian rhythms and defence responses in tomato. In addition to identifying these key transcription factors in tomato, the application of red light at night for one week not only reactivated key antioxidant enzymes at the gene and enzyme activity level at dawn but also contributed to a more efficient and successful defence against Botrytis cinerea infection.


Asunto(s)
Botrytis , Regulación de la Expresión Génica de las Plantas , Luz , Enfermedades de las Plantas , Solanum lycopersicum , Botrytis/fisiología , Solanum lycopersicum/microbiología , Solanum lycopersicum/genética , Solanum lycopersicum/efectos de la radiación , Solanum lycopersicum/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Ácido Salicílico/metabolismo , Ritmo Circadiano/fisiología , Ritmo Circadiano/efectos de la radiación , Reguladores del Crecimiento de las Plantas/metabolismo , Peróxido de Hidrógeno/metabolismo , Luz Roja
5.
Diagnostics (Basel) ; 14(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39061631

RESUMEN

Aim of the study was to investigate the demographic data and disease course characteristics of patients with Sjögren's syndrome (SS) and inflammatory joint pain of various origins and to search for factors that might help with the distinction of polyarthritis as an extraglandular manifestation and rheumatoid arthritis as an associated systemic autoimmune disorder. A total of 355 patients were retrospectively analyzed, 128 of whom served as controls (SS-C), while 159 had polyarthritis as an extraglandular symptom of Sjögren's syndrome (SS-pa) and 68 were diagnosed as having associated rheumatoid arthritis (SS-RA). The patients without any inflammatory joint manifestations were significantly older than the SS-pa patients, while, for the SS-RA group, the difference was not significant. The onset of joint pain appeared significantly earlier in the SS-RA patients. Regarding either extraglandular manifestations or associated autoimmune disorders, there were significant differences between the controls and both SS-pa and SS-RA groups, while no significant difference was found between the SS-pa and SS-RA groups. Thus, laboratory and imaging methods should be used to differentiate between the two conditions, but laboratory biomarkers are even more important for early diagnosis. A ROC curve analysis showed an acceptable diagnostic accuracy in differentiating between SS-pa and SS-RA patients using a binary logistic regression model, where highly positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) values, kidney involvement, and anti-Ro/SS-A positivity were shown to significantly raise the odds of having RA, whereas anti-La/SS-B positivity seemed to have a protective role, since it significantly decreased the odds of having it. Further biomarkers are needed to better classify SS patient cohorts with inflammatory joint pain of different origins and, consequently, different management requirements.

6.
Antibiotics (Basel) ; 13(6)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38927215

RESUMEN

The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions-amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide-and their 10-fold dilution series in tryptone soy broth (TSB) at 37 °C, over 12 days. Samples were collected immediately after preparation and on days 1, 2, 5, 7, 9, and 12, with active substance concentrations measured using ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry. The results indicated that among the ultrapure water stock solutions, neomycin, florfenicol, and potentiated sulfonamide maintained stability (>95%). Within the culture medium, florfenicol showed consistent stability (100%) throughout the study, potentiated sulfonamide experienced minor degradation (>85%), and neomycin underwent significant degradation. Amoxicillin, oxytetracycline, and colistin displayed considerable degradation in both solution types but were more stable in ultrapure water solutions. The stability of cefotaxime and enrofloxacin in ultrapure water solutions and in the medium was very similar when compared; however, 3.6% of the former and 88.7% of the latter remained detectable by day 12. These findings are crucial for minimum inhibitory concentration (MIC) assessments, especially in minimum bactericidal concentration (MBC) studies, and in experiments concerning long-term evolution and co-selection. This study underscores the necessity of stability assessments in culture media to validate future experimental outcomes.

7.
J Med Chem ; 67(10): 8261-8270, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38690886

RESUMEN

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [52Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [52Mn]Mn isotope. In comparison to DOTA-GA-trastuzumab, the BPPA-trastuzumab conjugate exhibits a labeling efficiency with [52Mn]Mn approximately 2 orders of magnitude higher. In female CB17 SCID mice bearing 4T1 (HER2-) and MDA-MB-HER2+ (HER2+) xenografts, [52Mn]Mn-BPPA-trastuzumab demonstrated superior uptake in HER2+ cells on day 3, with a 3-4 fold difference observed on day 7. Overall, the hexadentate BPPA chelator proves to be exceptional in binding Mn(II). Upon coupling with trastuzumab as a BFC ligand, it becomes an excellent imaging probe for HER2-positive tumors. [52Mn]Mn-BPPA-trastuzumab enables an extended imaging time window and earlier detection of HER2-positive tumors with superior tumor-to-background contrast.


Asunto(s)
Manganeso , Ratones SCID , Tomografía de Emisión de Positrones , Receptor ErbB-2 , Trastuzumab , Animales , Femenino , Ratones , Línea Celular Tumoral , Quelantes/química , Quelantes/síntesis química , Manganeso/química , Manganeso/metabolismo , Ratones Endogámicos BALB C , Ácidos Picolínicos/química , Tomografía de Emisión de Positrones/métodos , Radiofármacos/química , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Receptor ErbB-2/metabolismo , Distribución Tisular , Trastuzumab/química
8.
Entropy (Basel) ; 26(5)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38785635

RESUMEN

The focus of our research is the examination of Hermitian curves over finite fields, specifically concentrating on places of degree three and their role in constructing Hermitian codes. We begin by studying the structure of the Riemann-Roch space associated with these degree-three places, aiming to determine essential characteristics such as the basis. The investigation then turns to Hermitian codes, where we analyze both functional and differential codes of degree-three places, focusing on their parameters and automorphisms. In addition, we explore the study of subfield subcodes and trace codes, determining their structure by giving lower bounds for their dimensions. This presents a complex problem in coding theory. Based on numerical experiments, we formulate a conjecture for the dimension of some subfield subcodes of Hermitian codes. Our comprehensive exploration seeks to deepen the understanding of Hermitian codes and their associated subfield subcodes related to degree-three places, thus contributing to the advancement of algebraic coding theory and code-based cryptography.

9.
BMC Public Health ; 24(1): 1073, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632614

RESUMEN

INTRODUCTION: Problematic usage of the internet (PUI) is perhaps one of the most frequently studied phenomena of the 21st century receiving increasing attention in both scientific literature and the media. Despite intensive research there have been relatively few meaningful studies among elementary school students in Hungary and worldwide, who may be considered as a high-risk population with regard to problematic internet use. The aim of our study was to carry out a complex research focusing on the prevalence and risk factors of PUI among elementary school children aged 10-15 years (Grade 5-8). METHODS: Demographics included were gender, age, place of stay, type of residence, family type, parental education, start of internet use, used devices, daily internet use, purpose of internet use, internet accounts, ways of keeping in touch with friends and sporting activities. PUI was evaluated using the paper-based version of the Potentially Problematic Use of the Internet Questionnaire. RESULTS: Overall, 2000 paper-based questionnaires were successfully delivered and the final analysis included 1168 responses (overall response rate 58.4%). Mean age was 12.55 ± 1.24 years. Female gender (OR = 2.760, p = 0,006, CI 95% 0.065 to 0.384), younger age (11-12 years) (OR = 3.812, p < 0.001, 95% CI: 1.747-4.731), early exposure to the internet (OR = 3.466, p = 0.001, 95% CI 1.535-5.446), living in a small village (OR = 1.081, p = 0.002, 95% CI 1.041-1.186) urgency to answer online (OR = 4.677, p < 0.001, 95% CI: 2.714-6.639), decreased frequency of personal contact with friends (OR = 2.897, p = 0.004, 95% CI: 1.037-1.681), spending more than 6 h online (OR = 12.913, p < 0.001, 95% CI: 10.798-14.892), morning and nighttime internet use (OR = 3.846, p < 0.001, CI 95% 1.886-5.810) and never doing any sports (OR = 2.016, p = 0.044, 95% CI: 1.050-3.354) were independently associated with problematic internet use. CONCLUSIONS: Based on the results of our questionnaire survey more than 10% seemed to be problematic users in our study population, which is a relatively high rate. Early exposure to the internet as well as younger age were strongly related to this phenomenon. Duration of being online as well as daily time interval of internet use are important predisposing factors. Scarcely studied social factors such as being online at the expense of personal relationships and the lack of physical activity should be payed more attention to prevent the development of PUI.


Asunto(s)
Conducta Adictiva , Instituciones Académicas , Niño , Humanos , Femenino , Adolescente , Estudios Transversales , Hungría , Estudiantes , Encuestas y Cuestionarios , Internet , Conducta Adictiva/epidemiología
10.
Appl Spectrosc ; : 37028241239977, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38646777

RESUMEN

Circular dichroism (CD) spectroscopy is an analytical technique that measures the wavelength-dependent differential absorbance of circularly polarized light and is applicable to most biologically important macromolecules, such as proteins, nucleic acids, and carbohydrates. It serves to characterize the secondary structure composition of proteins, including intrinsically disordered proteins, by analyzing their recorded spectra. Several computational tools have been developed to interpret protein CD spectra. These methods have been calibrated and tested mostly on globular proteins with well-defined structures, mainly due to the lack of reliable reference structures for disordered proteins. It is therefore still largely unclear how accurately these computational methods can determine the secondary structure composition of disordered proteins. Here, we provide such a required reference data set consisting of model structural ensembles and matching CD spectra for eight intrinsically disordered proteins. Using this set of data, we have assessed the accuracy of several published CD prediction and secondary structure estimation tools, including our own CD analysis package, SESCA. Our results show that for most of the tested methods, their accuracy for disordered proteins is generally lower than for globular proteins. In contrast, SESCA, which was developed using globular reference proteins, but was designed to be applicable to disordered proteins as well, performs similarly well for both classes of proteins. The new reference data set for disordered proteins should allow for further improvement of all published methods.

11.
J Int Med Res ; 52(4): 3000605241237876, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38606757

RESUMEN

Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Trastornos Relacionados con Cocaína , Cocaína , Granulomatosis con Poliangitis , Femenino , Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Trastornos Relacionados con Cocaína/complicaciones , Trastornos Relacionados con Cocaína/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones
12.
Arch Virol ; 169(5): 100, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630394

RESUMEN

In this study, a novel genotype of genogroup X (GX) sapovirus (family Caliciviridae) was detected in the small intestinal contents of a golden jackal (Canis aureus) in Hungary and characterised by viral metagenomics and next-generation sequencing techniques. The complete genome of the detected strain, GX/Dömsöd/DOCA-11/2020/HUN (PP105600), is 7,128 nt in length. The ORF1- and ORF2-encoded viral proteins (NSP, VP1, and VP2) have 98%, 95%, and 88% amino acid sequence identity to the corresponding proteins of genogroup GX sapoviruses from domestic pigs, but the nucleic acid sequence identity values for their genes are significantly lower (83%, 77%, and 68%). During an RT-PCR-based epidemiological investigation of additional jackal and swine samples, no other GX strains were detected, but a GXI sapovirus strain, GXI/Tótfalu/WBTF-10/2012/HUN (PP105601), was identified in a faecal sample from a wild boar (Sus scrofa). We report the detection of members of two likely underdiagnosed groups of sapoviruses (GX and GXI) in a golden jackal and, serendipitously, in a wild boar in Europe.


Asunto(s)
Caliciviridae , Canidae , Sapovirus , Animales , Porcinos , Sapovirus/genética , Chacales , Hungría/epidemiología , Genotipo , Sus scrofa
13.
Magy Onkol ; 68(1): 27-35, 2024 Mar 14.
Artículo en Húngaro | MEDLINE | ID: mdl-38484373

RESUMEN

Pineal region tumors account for less than 1% of adult supratentorial tumors. Their treatment requires a multimodality approach. Previously, the treatment of choice was direct surgery, which is associated with high surgical risk. Advances in minimally invasive techniques and onco-radiotherapy offer a safe and multimodal personalized therapy. The aim of our study was to describe the practice of our Institute based on combined endoscopic and radiotherapy techniques. We performed a retrospective clinical study. We processed data from 23 adult patients who underwent endoscopic third ventricle fenestration and pineal tumor biopsy between 2014 and 2023. Descriptive statistics, t-test, Fisher's exact test and Kaplan-Meier analysis were performed. Clinical improvement with endoscopic intervention was achieved in 78.3% of cases. Significant increase in preoperative performance status was observed in the postoperative period (p=2.755e-5), and radiotherapy resulted in regression or stable disease. Our results suggest a safe treatment with good clinical outcome and an excellent alternative to direct surgery.


Asunto(s)
Neoplasias Encefálicas , Glándula Pineal , Pinealoma , Adulto , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Terapia Combinada , Glándula Pineal/cirugía , Glándula Pineal/patología , Pinealoma/radioterapia , Pinealoma/cirugía , Pinealoma/patología , Estudios Retrospectivos
14.
Clin Chim Acta ; 553: 117747, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38154766

RESUMEN

BACKGROUND: A major challenge of the HEp-2 cell-based indirect immunofluorescence (IIF) assays is the correct identification of the individual anti-nuclear antibodies (ANAs) if more than one is present in a sample. We created artificial mixes by pooling two different samples with a single autoantibody in different titers. Comparison of the expected and observed patterns and titers clarifies the interference between the two tested ANAs. METHODS: Serum samples with a single homogeneous or speckled ANA pattern were serially diluted and mixed in 16 combinations, providing end-point titers of 1:5,120 to 1:80 for both patterns. These mixes were tested by a HEp-2 IIF assay and were evaluated by conventional evaluation, the EUROPattern (EPa) system and on-screen analysis. RESULTS: Homogeneous pattern can alter the identification of the speckled pattern much more than vice versa, but both has an interfering effect on the other. The effect of the interfering on the tested pattern was higher if the titer of the former one was higher. The pattern recognition efficacy of conventional and the on-screen evaluation was similar and superior compared to the EPa analysis. CONCLUSIONS: The application of artificial mixed samples can help the evaluation of the efficacy of manual and computer-aided ANA HEp-2 pattern recognition.


Asunto(s)
Anticuerpos Antinucleares , Enfermedades Autoinmunes , Humanos , Autoanticuerpos , Técnica del Anticuerpo Fluorescente Indirecta , Computadores
15.
Sci Rep ; 13(1): 21176, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040783

RESUMEN

The cestode, Echinococcus multilocularis, is one of the most threatening parasitic challenges in the European Union. Despite the warming climate, the parasite intensively spread in Europe's colder and warmer regions. Little is known about the expansion of E. multilocularis in the Balkan region. Ordinary least squares, geographically weighted and multi-scale geographically weighted regressions were used to detect global and local drivers that influenced the prevalence in red foxes and golden jackals in the southwestern part of Hungary. Based on the study of 391 animals, the overall prevalence exceeded 18% (in fox 15.2%, in jackal 21.1%). The regression models revealed that the wetland had a global effect (ß = 0.391, p = 0.006). In contrast, on the local scale, the mean annual precipitation (ß = 0.285, p = 0.008) and the precipitation seasonality (ß = - 0.211, p = 0.014) had statistically significant effects on the infection level. The geospatial models suggested that microclimatic effects might compensate for the disadvantages of a warmer Mediterranean climate. This study calls attention to fine-scale analysis and locally acting environmental factors, which can delay the expected epidemic fade-out. The findings of our study are suggested to consider in surveillance strategies.


Asunto(s)
Equinococosis , Echinococcus multilocularis , Animales , Peninsula Balcánica/epidemiología , Equinococosis/epidemiología , Equinococosis/veterinaria , Equinococosis/parasitología , Zorros , Prevalencia
16.
Sci Rep ; 13(1): 21951, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-38081944

RESUMEN

Huntington's disease (HD) is a neurodegenerative disorder caused by a dominant gain-of-function mutation in the huntingtin gene, resulting in an elongated polyglutamine repeat in the mutant Huntingtin (mHtt) that mediates aberrant protein interactions. Previous studies implicated the ubiquitin-proteasome system in HD, suggesting that restoring cellular proteostasis might be a key element in suppressing pathology. We applied genetic interaction tests in a Drosophila model to ask whether modulating the levels of deubiquitinase enzymes affect HD pathology. By testing 32 deubiquitinase genes we found that overexpression of Yod1 ameliorated all analyzed phenotypes, including neurodegeneration, motor activity, viability, and longevity. Yod1 did not have a similar effect in amyloid beta overexpressing flies, suggesting that the observed effects might be specific to mHtt. Yod1 overexpression did not alter the number of mHtt aggregates but moderately increased the ratio of larger aggregates. Transcriptome analysis showed that Yod1 suppressed the transcriptional effects of mHtt and restored the expression of genes involved in neuronal plasticity, vesicular transport, antimicrobial defense, and protein synthesis, modifications, and clearance. Furthermore, Yod1 overexpression in HD flies leads to the upregulation of genes involved in transcriptional regulation and synaptic transmission, which might be part of a response mechanism to mHtt-induced stress.


Asunto(s)
Drosophila , Enfermedad de Huntington , Animales , Péptidos beta-Amiloides/genética , Enzimas Desubicuitinizantes/genética , Modelos Animales de Enfermedad , Drosophila/genética , Drosophila/metabolismo , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Enfermedad de Huntington/metabolismo , Mutación , Ubiquitina/genética
17.
Viruses ; 15(12)2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-38140540

RESUMEN

The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus Sincitial Respiratorio Humano , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Rociadores Nasales , SARS-CoV-2
18.
Environ Technol ; : 1-12, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37970831

RESUMEN

The increasing waste generation trends resulted in growing attention to the technologies that aim to reduce or prevent landfilling. The pyrolysis and gasification of refuse-derived fuel (RDF) allow waste to be turned into new raw materials, like pyrolysis gas and syngas. However, the wet gas cleaning processes result in the production of highly contaminated liquid waste. Phenolic compounds are common constituents of this wastewater and often appear in the wastewater of other industries as well. In this research, the laboratory-scale steam gasification of an RDF char was performed to produce syngas and adsorbent simultaneously. The RDF was previously pyrolyzed at 700 °C maximum temperature in a Hungarian pyrolysis pilot plant with approximately 120 kg h-1 capacity. In this thermal waste processing plant, the pyrolysis gas is already utilised by burning, but currently, the char ends up in landfills. The gasification of char samples was examined with different steam-to-carbon ratios (0.56, 0.84, and 1.12) and duration (30, 60, and 120 min) at 900 °C. Following gasification, the phenol removal capability of the solid by-products was investigated. The results show that its composition and energetic properties make the produced syngas more suitable to use as a raw material in the chemical industry rather than a fuel. At lower concentrations, the effectiveness of the solid by-product for phenol removal was comparable to commercial activated carbon. These are promising results about producing activated carbon from waste without any chemical treatment.

19.
Microorganisms ; 11(10)2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37894182

RESUMEN

A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.

20.
Materials (Basel) ; 16(19)2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37834707

RESUMEN

The harmful effects of wear can be reduced through proper lubrication of the frictional parts. When exposed to excessive loads, the lubricant film is displaced from the surfaces, and even the adhesive lubricant layer may rupture. Additives known as Extreme Pressure (EP) are frequently incorporated into lubricants to minimise wear and avert seizures under high temperature and pressure. Mechanistically, these additives generate a film on the surface through chemisorption. These additives are extensively applied in various lubricants, with the largest quantities being employed in metalworking fluids and lubricating greases. Sulfurized vegetable oils and their derivates can be used as EP additives for lubricants. To conduct the investigations, sulfurized additives were synthesized using different vegetable-based oils and fatty acid esters, and alpha-olefins. In this study, the Four-ball test results were compared to gain a more accurate comprehension of how various raw-material-based additives influence wear and friction. The goal was to select raw materials that could be used with favorable results for the production of EP additives. The objective was to achieve a minimum Four-ball weld load parameter of 2000 N. The experiments revealed that the functional impacts of the synthesized samples are dependent on the type of raw materials employed. Based on the experimental data and the stated criteria, the examined raw materials were found to be suitable for the synthesis of EP additives.

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