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1.
Artículo en Inglés | MEDLINE | ID: mdl-39090366

RESUMEN

OBJECTIVES: Communities of color might disproportionately experience long-term consequences of COVID-19, known as Long COVID. We sought to understand the awareness of and experiences with Long COVID among African American/Black (AA/B), Hispanic/Latino (H/L), and Indigenous (Native) adults (18 + years of age) in Arizona who previously tested positive for COVID-19. METHODS: Between December 2022 and April 2023, the Arizona Community Engagement Alliance (AZCEAL) conducted 12 focus groups and surveys with 65 AA/B, H/L and Native community members. Data from focus groups were analyzed using thematic analysis to identify emerging issues. Survey data provided demographic information about participants and quantitative assessments of Long COVID experiences were used to augment focus group data. RESULTS: Study participants across all three racial/ethnic groups had limited to no awareness of the term Long COVID, yet many described experiencing or witnessing friends and family endure physical symptoms consistent with Long COVID (e.g., brain fog, loss of memory, fatigue) as well as associated mental health issues (e.g., anxiety, worry, post-traumatic stress disorder). Participants identified a need for Long COVID mental health and other health resources, as well as increased access to Long COVID information. CONCLUSION: To prevent Long COVID health inequities among AA/B, H/L, and Native adults living in AZ, health-related organizations and providers should increase access to culturally relevant, community-based Long COVID-specific information, mental health services, and other health resources aimed at serving these populations.

2.
Neurology ; 103(3): e209708, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38991193

RESUMEN

The clinical assessment of patients with proximal muscle weakness represents a frequent yet intricate challenge. We present the case of a 60-year-old woman who experienced a progressive, symmetrical weakness in proximal limbs and bulbar muscles over 6 months. Notable clinical findings included bilateral ophthalmoparesis; widespread muscle atrophy; and pronounced weakness in craniobulbar, cervical, and proximal muscles, more severe than in distal ones. We elucidate a methodical diagnostic approach, focusing on constructing a comprehensive differential diagnosis and identifying potential causes of proximal muscle weakness. Special emphasis is placed on exploring the etiologies in cases presenting with both progressive muscle weakness and ophthalmoparesis. We further describe the role of muscle biopsy results and their integration with genetic testing outcomes.


Asunto(s)
Debilidad Muscular , Oftalmoplejía , Humanos , Femenino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/diagnóstico , Oftalmoplejía/diagnóstico , Razonamiento Clínico , Diagnóstico Diferencial , Progresión de la Enfermedad
3.
Mol Cell ; 84(13): 2490-2510.e9, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38996459

RESUMEN

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.


Asunto(s)
Dominio BTB-POZ , Factores de Transcripción , Proteínas de Xenopus , Animales , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/genética , Cristalografía por Rayos X , Células HEK293 , Modelos Moleculares , Unión Proteica , Multimerización de Proteína , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/química , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Xenopus laevis , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/química
4.
J Neurosci ; 44(30)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38897723

RESUMEN

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.


Asunto(s)
Conducta Alimentaria , Habénula , Luz , Animales , Masculino , Ratones , Habénula/fisiología , Conducta Alimentaria/fisiología , Núcleo Dorsal del Rafe/fisiología , Humanos , Ratones Endogámicos C57BL , Ingestión de Alimentos/fisiología , Vías Nerviosas/fisiología , Ratas , Neuronas Serotoninérgicas/fisiología , Red Nerviosa/fisiología , Oscuridad
5.
Heliyon ; 10(7): e27820, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560215

RESUMEN

Marine macroalgae are the habitat of epiphytic bacteria and provide several conditions for a beneficial biological interaction to thrive. Although Bacillus is one of the most abundant epiphytic genera, genomic information on marine macroalgae-associated Bacillus species remains scarce. In this study, we further investigated our previously published genome of the epiphytic strain Bacillus altitudinis 19_A to find features that could be translated to potential metabolites produced by this microorganism, as well as genes that play a role in its interaction with its macroalgal host. To achieve this goal, we performed a pan-genome analysis of Bacillus sp. and a codon bias assessment, including the genome of the strain Bacillus altitudinis 19_A and 29 complete genome sequences of closely related Bacillus strains isolated from soil, marine environments, plants, extreme environments, air, and food. This genomic analysis revealed that Bacillus altitudinis 19_A possessed unique genes encoding proteins involved in horizontal gene transfer, DNA repair, transcriptional regulation, and bacteriocin biosynthesis. In this comparative analysis, codon bias was not associated with the habitat of the strains studied. Some accessory genes were identified in the Bacillus altitudinis 19_A genome that could be related to its epiphytic lifestyle, as well as gene clusters for the biosynthesis of a sporulation-killing factor and a bacteriocin, showing their potential as a source of antimicrobial peptides. Our results provide a comprehensive view of the Bacillus altitudinis 19_A genome to understand its adaptation to the marine environment and its potential as a producer of bioactive compounds.

6.
Int J Legal Med ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613625

RESUMEN

Chile had a violent military coup (1973-1990) that resulted in 3,000 victims declared detained, missing or killed; many are still missing and unidentified. Currently, the Human Rights Unit of the Forensic Medical Service in Chile applies globally recognised forensic anthropological approaches, but many of these methods have not been validated in a Chilean sample. As current research has demonstrated population-specificity with extant methods, the present study aims to validate sex estimation methods in a Chilean population and thereafter establish population-specific equations. A sample of 265 os coxae of known age and sex of adult Chileans from the Santiago Subactual Osteology Collection were analysed. Visual assessment and scoring of the pelvic traits were performed in accordance with the Phenice (1969) and Klales et al. (2012) methods. The accuracy of Phenice (1969) in the Chilean sample was 96.98%, with a sex bias of 7.68%. Klales et al. (2012) achieved 87.17% accuracy with a sex bias of -15.39%. Although both methods showed acceptable classification accuracy, the associated sex bias values are unacceptable in forensic practice. Therefore, six univariate and eight multivariate predictive models were formulated for the Chilean population. The most accurate univariate model was the ventral arc at 96.6%, with a sex bias of 5.2%. Classification accuracy using all traits was 97.0%, with a sex bias of 7.7%. This study provides Chilean practitioners a population-specific morphoscopic standard with associated classification probabilities acceptable to accomplish legal admissibility requirements in human rights and criminal cases specific to the second half of the 20th century.

7.
Hum Gene Ther ; 35(5-6): 163-176, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38386500

RESUMEN

Delivering vectorized information into cells with the help of viruses has been of high interest to fundamental and applied science, and bears significant therapeutic promise. Human adenoviruses (HAdVs) have been at the forefront of gene delivery for many years, and the subject of intensive development resulting in several generations of agents, including replication-competent, -defective or retargeted vectors, and recently also helper-dependent (HD), so-called gutless vectors lacking any viral protein coding information. While it is possible to produce HD-AdVs in significant amounts, physical properties of these virus-like particles and their efficiency of transduction have not been addressed. Here, we used single-cell and single virus particle assays to probe the effect of genome length on HAdV-C5 vector transduction. Our results demonstrate that first-generation C5 vectors lacking the E1/E3 regions of the viral genome as well as HD-AdV-C5 particles with a wild type (wt) ∼36 kbp or an undersized double-strand DNA genome are similar to human adenovirus C5 (HAdV-C5) wt regarding attachment to human lung epithelial cells, endocytic uptake, endosome penetration and dependency on the E3 RING ubiquitin ligase Mind Bomb 1 for DNA uncoating at the nuclear pore complex. Atomic force microscopy measurements of single virus particles indicated that small changes in the genome length from 94% to 103% of HAdV-C5 have no major impact on physical and mechanical features of AdV vectors. In contrast, an HD-AdV-C5 with ∼30 kbp genome was slightly stiffer and less heat-resistant than the other particles, despite comparable entry and transduction efficiencies in tissue culture cell lines, including murine alveolar macrophage-like Max-Planck-Institute (MPI)-2 cells. Together, our in vitro studies reinforce the use of HD-AdV vectors for effective single round gene delivery. The results illustrate how physical properties and cell entry behavior of single virus particles can provide functional information for anticipated therapeutic vector applications.


Asunto(s)
Adenoviridae , Adenovirus Humanos , Animales , Humanos , Ratones , Adenoviridae/genética , Adenovirus Humanos/genética , Línea Celular , Vectores Genéticos , ADN
8.
J Med Virol ; 96(2): e29431, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38293752

RESUMEN

The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV  polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.


Asunto(s)
Queratosis , Infecciones por Papillomavirus , Verrugas , Humanos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Virus del Papiloma Humano , Estudios Prospectivos , Verrugas/epidemiología , Papillomaviridae/genética , ADN Viral/genética , ADN Viral/análisis
9.
Diagnosis (Berl) ; 11(1): 97-101, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37747801

RESUMEN

OBJECTIVES: Little is known about how patients perceive diagnostic uncertainty. We sought to understand how patients and care partners perceive uncertainty in an emergency or urgent care setting, where making a final diagnosis is often not possible. METHODS: We administered a survey to a nationally representative panel on patient-reported diagnostic excellence in an emergency department or urgent care setting. The survey included items specific to perceived diagnostic excellence, visit characteristics, and demographics. We analyzed responses to two open-ended questions among those who reported uncertainty in the explanation they were given. Themes were identified using an inductive approach, and compared by whether respondents agreed or disagreed the explanation they were given was true. RESULTS: Of the 1,116 respondents, 106 (10 %) reported that the care team was not certain in the explanation of their health problem. Five themes were identified in the open-ended responses: poor communication (73 %), uncertainty made transparent (10 %), incorrect information provided (9 %), inadequate testing equipment (4 %), and unable to determine (4 %). Of the respondents who reported uncertainty, 21 % (n=22/106) reported the explanation of their problem given was not true. CONCLUSIONS: The findings of this analysis suggest that the majority of patients and their care partners do not equate uncertainty with a wrong explanation of their health problem, and that poor communication was the most commonly cited reason for perceived uncertainty.


Asunto(s)
Cuidadores , Servicio de Urgencia en Hospital , Humanos , Incertidumbre , Pacientes , Atención Ambulatoria
10.
Med Decis Making ; 44(1): 102-111, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37965762

RESUMEN

OBJECTIVES: In the context of validating a measure of patient report specific to diagnostic accuracy in emergency department or urgent care, this study investigates patients' and care partners' perceptions of diagnoses as accurate and explores variations in how they reason while they assess accuracy. METHODS: In February 2022, we surveyed a national panel of adults who had an emergency department or urgent care visit in the past month to test a patient-reported measure. As part of the survey validation, we asked for free-text responses about why the respondents indicated their (dis)agreement with 2 statements comprising patient-reported diagnostic accuracy: 1) the explanation they received of the health problem was true and 2) the explanation described what to expect of the health problem. Those paired free-text responses were qualitatively analyzed according to themes created inductively. RESULTS: A total of 1,116 patients and care partners provided 982 responses coded into 10 themes, which were further grouped into 3 reasoning types. Almost one-third (32%) of respondents used only corroborative reasoning in assessing the accuracy of the health problem explanation (alignment of the explanation with either test results, patients' subsequent health trajectory, their medical knowledge, symptoms, or another doctor's opinion), 26% used only perception-based reasoning (perceptions of diagnostic process, uncertainty around the explanation received, or clinical team's attitudes), and 27% used both types of reasoning. The remaining 15% used general beliefs or nonexplicated logic (used only about accurate diagnoses) and combinations of general reasoning with perception-based and corroborative. CONCLUSIONS: Patients and care partners used multifaceted reasoning in their assessment of diagnostic accuracy. IMPLICATIONS: As health care shifts toward meaningful diagnostic co-production and shared decision making, in-depth understanding of variations in patient reasoning and mental models informs use in clinical practice. HIGHLIGHTS: An analysis of 982 responses examined how patients and care partners reason about the accuracy of diagnoses they received in emergency or urgent care.In reasoning, people used their perception of the process and whether the diagnosis matched other factual information they have.We introduce "patient reasoning" in the diagnostic measurement context as an area of further research to inform diagnostic shared decision making and co-production of health.


Asunto(s)
Cuidadores , Servicios Médicos de Urgencia , Adulto , Humanos , Solución de Problemas , Servicio de Urgencia en Hospital , Pacientes
11.
Pancreas ; 52(4): e241-e248, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37801622

RESUMEN

OBJECTIVES: To analyze if antithrombin III (AT-III) and d -dimer levels at admission and at 24 hours can predict acute pancreatitis (AP) progression to moderately severe AP (MSAP) to severe AP (SAP) and to determine their predictive value on the development of necrosis, infected necrosis, organ failure, and mortality. METHODS: Prospective observational study conducted in patients with mild AP in 2 tertiary hospitals (2015-2017). RESULTS: Three hundred forty-six patients with mild AP were included. Forty-four patients (12.7%) evolved to MSAP/SAP. Necrosis was detected in 36 patients (10.4%); in 10 (2.9%), infection was confirmed. Organ failure was recorded in 9 patients (2.6%), all of whom died. Those who progressed to MSAP/SAP showed lower AT-III levels; d -dimer and C-reactive protein (CRP) levels increased. The best individual marker for MSAP/SAP at 24 hours is CRP (area under the curve [AUC], 0.839). Antithrombin III (AUC, 0.641), d -dimer (AUC, 0.783), and creatinine added no benefit compared with CRP alone. Similar results were observed for patients who progressed to necrosis, infected necrosis, and organ failure/death. CONCLUSION: Low AT-III and high d -dimer plasma levels at 24 hours after admission were significantly associated with MSAP/SAP, although their predictive ability was low. C-reactive protein was the best marker tested. CLINICAL STUDY IDENTIFIER: ClinicalTrials.gov NCT02373293.


Asunto(s)
Pancreatitis , Humanos , Estudios Prospectivos , Proteína C-Reactiva , Enfermedad Aguda , Antitrombina III , Pronóstico , Índice de Severidad de la Enfermedad , Anticoagulantes , Necrosis , Biomarcadores
12.
Oral Dis ; 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37877476

RESUMEN

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.

13.
Vaccine X ; 15: 100372, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37693843

RESUMEN

The study compared immunity to the original SARS-CoV-2 virus (Wuhan) and the Omicron variant using neutralizing antibodies (NAbs), that provide a good approximation of protective immunity. The results might help determine immunization strategies. DESIGN AND METHODS: Unlike previous studies, we analyzed NAbs in a random sample of 110 IgG positive sera from individuals who participated in a population-based seroprevalence transversal study, carried out in May 2022 in two Chilean cities, a country with high vaccination coverage. RESULTS: Our findings indicate that 98.2% of individuals had NAbs against Wuhan, 65.5% against Omicron, and 32.7% tested positive for Wuhan but not Omicron. Factors influencing protective immunity included a prior natural infection and the number of vaccines received. NAbs titers against the original virus were high, demonstrating vaccine effectiveness in the population. However, the level of antibodies decreased when measuring NAbs against Omicron, particularly among older individuals, indicating a decline in vaccine protection. Previous COVID-19 episodes acted as a natural booster, increasing NAbs titers against both virus strains. CONCLUSIONS: Protective immunity against the original Wuhan SARS-CoV-2 virus is reduced when compared to Omicron variant. Updating vaccine to target emerging variants and continued monitoring of effectiveness at the population level are necessary.

14.
J Neurol Surg Rep ; 84(3): e116-e123, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37771654

RESUMEN

The aim of this report is to describe TransOrbital NeuroEndoscopic Surgery (TONES) as a safe alternative for obtaining a cavernous sinus (CS) biopsy. We describe this technique in a patient with a diffuse large B cell lymphoma mimicking Tolosa-Hunt's syndrome. Articles were gathered querying PubMed, Embase, and Scopus databases with terms related to a "transorbital neuroendoscopic approach." The literature search was performed by two independent authors (N.L.F. and J.R.), with inconsistencies resolved by the senior author (M.M.D.V.). After screening abstracts for relevance, full-length articles were reviewed for pertinent variables. A comparison was conducted with the illustrative case of a 69-year-old woman who presented to the emergency department with vertigo, ophthalmoplegia, and diplopia for 2 months. A brain magnetic resonance imaging revealed an infiltrative lesion at the left CS. A presumptive diagnosis of Tolosa-Hunt syndrome was made, but a confirmatory biopsy was performed using TONES. Based on our cadaveric study, literature review, and case report, the TONES approach was safe, effective for tissue diagnosis, and associated with minor morbidity and reduced hospital stay. Additional prospective studies are required to study its viability and safety in a larger group of patients.

15.
Cir Esp (Engl Ed) ; 101(10): 701-707, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37748643

RESUMEN

INTRODUCTION: Incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the capacity to become malignant, from true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are >6-10 mm, growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. Most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyse whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. METHODS: Retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study has been approved by the Clinical Research Ethics Committee of our hospital. RESULTS: We included 124 patients in our study. An elective laparoscopic cholecystectomy was performed in all of them. The mean age was 55,4 years and 61% were women. Of all patients, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2,4%). All of them were tubular adenomas. The rest of patients were false positives (97,6%). The adenoma size was 11, 6 and 5 mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. CONCLUSION: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. Validation of other complementary tests for the diagnosis of gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Enfermedades de la Vesícula Biliar , Neoplasias de la Vesícula Biliar , Neoplasias Gastrointestinales , Pólipos , Femenino , Humanos , Masculino , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Colecistectomía , Neoplasias Colorrectales/cirugía , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Enfermedades de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias Gastrointestinales/cirugía , Pólipos/diagnóstico por imagen , Pólipos/cirugía , Estudios Prospectivos , Ultrasonografía , Estudios Retrospectivos
16.
Biol Res ; 56(1): 21, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37147738

RESUMEN

BACKGROUND: Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.


Asunto(s)
Músculo Esquelético , Complejo de la Endopetidasa Proteasomal , Complejo de la Endopetidasa Proteasomal/metabolismo , Proliferación Celular/fisiología , Músculo Esquelético/metabolismo , Células Madre , Diferenciación Celular , Ubiquitinas/metabolismo , Desarrollo de Músculos/fisiología , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX7/metabolismo
17.
Vaccines (Basel) ; 11(5)2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37243116

RESUMEN

Chronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transplant (KT) and 52 on hemodialysis without prior COVID-19. The patients were assessed for humoral and cellular immune responses after four months of an anti-SARS-CoV-2 primary two-dose vaccination scheme (CoronaVac or BNT162b2) and one month after a booster third dose of BNT162b2 vaccine. We identified poor cellular and humoral immune responses in the CKD patients after a primary vaccination scheme, and these responses were improved by a booster. Robust polyfunctional CD4+ T cell responses were observed in the KT patients after a booster, and this could be attributed to a higher proportion of the patients having been vaccinated with homologous BNT162b2 schemes. However, even after the booster, the KT patients exhibited lower neutralizing antibodies, attributable to specific immunosuppressive treatments. Four patients suffered severe COVID-19 despite three-dose vaccination, and all had low polyfunctional T-cell responses, underscoring the importance of this functional subset in viral protection. In conclusion, a booster dose of SARS-CoV-2 mRNA vaccine in CKD patients improves the impaired humoral and cellular immune responses observed after a primary vaccination scheme.

18.
Sci Adv ; 9(14): eade9910, 2023 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-37027464

RESUMEN

Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entry.


Asunto(s)
Adenovirus Humanos , Cápside , Humanos , Cápside/metabolismo , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/metabolismo , Adenoviridae/genética , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Adenovirus Humanos/metabolismo
19.
iScience ; 26(4): 106382, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37034985

RESUMEN

Building a sustainable human habitat on the Moon requires advances in excavation, paving, and additive manufacturing to construct landing pads, surface transportation arteries, resilient shelters, and scientific outposts. Construction of infrastructure elements on the lunar surface necessitates exploration of the interfacial reactivity of locally sourced regolith and the adaptation of Earth-based construction techniques. Various crosslinking frameworks and sintering methods have been proposed as a means of consolidating lunar regolith into load-bearing structures but each have challenges related to incomplete understanding of reaction chemistry, excessive thermal budgets, and lack of universal applicability to different mineral components of regolith. We describe here a versatile experimental and computational study of the consolidation of a regolith simulant through formation of siloxane networks enmeshing mineral particles by surface dissolution-precipitation and polycondensation reactions. Furthermore, by tailoring the rheological properties of the formulation an additive manufacturing feedstock can be developed for the construction of lunar infrastructure.

20.
Biotechnol Rep (Amst) ; 37: e00788, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36874444

RESUMEN

Marine macroalgae are being recognized as reservoirs of biologically active compounds, as their surfaces are susceptible to the colonization of microorganisms which can produce enzymes with a wide range of molecular architectures. Among these bacteria, Achromobacter is responsible for the biosynthesis of laccases. In this research, we performed a bioinformatic pipeline to annotate the sequenced complete genome of the epiphytic bacterium Achromobacter denitrificans strain EPI24, from the macroalgal surface of the Ulva lactuca species; this strain showed laccase activity which has been previously assessed on plate assays. The genome of A. denitrificans strain EPI24 has a size of ∼6.95 Mb, a GC content of 67.33%, and 6,603 protein-coding genes. The functional annotation of the A. denitrificans strain EPI24 genome confirmed the presence of genes encoding for laccases, which could have functional properties of interest in processes such as the biodegradation of phenolic compounds under versatile and efficient conditions.

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