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1.
Cell ; 163(6): 1484-99, 2015 Dec 03.
Article in English | MEDLINE | ID: mdl-26638075

ABSTRACT

The centrosome is the primary microtubule organizing center of the cells and templates the formation of cilia, thereby operating at a nexus of critical cellular functions. Here, we use proximity-dependent biotinylation (BioID) to map the centrosome-cilium interface; with 58 bait proteins we generate a protein topology network comprising >7,000 interactions. Analysis of interaction profiles coupled with high resolution phenotypic profiling implicates a number of protein modules in centriole duplication, ciliogenesis, and centriolar satellite biogenesis and highlights extensive interplay between these processes. By monitoring dynamic changes in the centrosome-cilium protein interaction landscape during ciliogenesis, we also identify satellite proteins that support cilia formation. Systematic profiling of proximity interactions combined with functional analysis thus provides a rich resource for better understanding human centrosome and cilia biology. Similar strategies may be applied to other complex biological structures or pathways.


Subject(s)
Centrosome/metabolism , Cilia/metabolism , Protein Interaction Maps , Biotinylation , Cell Cycle , Humans , Microtubule-Organizing Center/metabolism
2.
Biochem Soc Trans ; 52(1): 279-289, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38385536

ABSTRACT

Diet is currently recognized as a major modifiable agent of human health. In particular, dietary nitrate has been increasingly explored as a strategy to modulate different physiological mechanisms with demonstrated benefits in multiple organs, including gastrointestinal, cardiovascular, metabolic, and endocrine systems. An intriguing exception in this scenario has been the brain, for which the evidence of the nitrate benefits remains controversial. Upon consumption, nitrate can undergo sequential reduction reactions in vivo to produce nitric oxide (•NO), a ubiquitous paracrine messenger that supports multiple physiological events such as vasodilation and neuromodulation. In the brain, •NO plays a key role in neurovascular coupling, a fine process associated with the dynamic regulation of cerebral blood flow matching the metabolic needs of neurons and crucial for sustaining brain function. Neurovascular coupling dysregulation has been associated with neurodegeneration and cognitive dysfunction during different pathological conditions and aging. We discuss the potential biological action of nitrate on brain health, concerning the molecular mechanisms underpinning this association, particularly via modulation of •NO-dependent neurovascular coupling. The impact of nitrate supplementation on cognitive performance was scrutinized through preclinical and clinical data, suggesting that intervention length and the health condition of the participants are determinants of the outcome. Also, it stresses the need for multimodal quantitative studies relating cellular and mechanistic approaches to function coupled with behavior clinical outputs to understand whether a mechanistic relationship between dietary nitrate and cognitive health is operative in the brain. If proven, it supports the exciting hypothesis of cognitive enhancement via diet.


Subject(s)
Neurovascular Coupling , Humans , Neurovascular Coupling/physiology , Nitrates/pharmacology , Nitric Oxide/metabolism , Dietary Supplements , Cognition
3.
J Neurovirol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935226

ABSTRACT

After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.

4.
Hum Reprod ; 39(3): 612-622, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38305414

ABSTRACT

STUDY QUESTION: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and environmental factors leads to the disease onset and progression. At the genetic level, genome-wide association studies (GWASs) allow the analysis of millions of genetic variants across the genome in a hypothesis-free manner, as a valuable tool for identifying susceptibility risk loci. However, little is known about the specific role of non-genetic factors and their influence on the genetic determinants in this type of conditions. STUDY DESIGN, SIZE, DURATION: Case-control genetic association analyses were performed including a total of 912 SPGF cases and 1360 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had European ancestry (Iberian and German). SPGF cases were diagnosed during the last decade either with idiopathic non-obstructive azoospermia (n = 547) or with idiopathic non-obstructive oligozoospermia (n = 365). Case-control genetic association analyses were performed by logistic regression models considering the generation as a covariate and by in silico functional characterization of the susceptibility genomic regions. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis revealed 13 novel genetic association signals with SPGF, with eight of them being independent. The observed associations were mostly explained by the interaction between each lead variant and the age-group. Additionally, we established links between these loci and diverse non-genetic factors, such as toxic or dietary habits, respiratory disorders, and autoimmune diseases, which might potentially influence the genetic architecture of idiopathic SPGF. LARGE SCALE DATA: GWAS data are available from the authors upon reasonable request. LIMITATIONS, REASONS FOR CAUTION: Additional independent studies involving large cohorts in ethnically diverse populations are warranted to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Overall, this study proposes an innovative strategy to achieve a more precise understanding of conditions such as SPGF by considering the interactions between a variable exposome through different generations and genetic predisposition to complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)" (ref. PY20_00212, P20_00583), the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. PID2020-120157RB-I00 funded by MCIN/ AEI/10.13039/501100011033), and the 'Proyectos I+D+i del Programa Operativo FEDER 2020' (ref. B-CTS-584-UGR20). ToxOmics-Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, is also partially supported by the Portuguese Foundation for Science and Technology (Projects: UIDB/00009/2020; UIDP/00009/2020). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Azoospermia , Oligospermia , Male , Humans , Genome-Wide Association Study , Genetic Predisposition to Disease , Azoospermia/genetics , Oligospermia/genetics , Environmental Exposure
5.
Org Biomol Chem ; 22(11): 2252-2263, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38390694

ABSTRACT

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost-effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live-dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations.


Subject(s)
Fluorescent Dyes , Microscopy , Cell Survival
6.
Neurosurg Rev ; 47(1): 518, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39215813

ABSTRACT

Regarding intracranial aneurysm treatment, the clip versus coil debate remains inconclusive and lacking studies in Brazil. To examine trends in the management of intracranial aneurysms in Brazil over time, both ruptured and unruptured. A descriptive and exploratory study was conducted based on data of neurovascular procedures for aneurysm treatment using the Brazilian Public Health System database (DATASUS). The variables analyzed were the number of procedures, mortality rates, length of hospital stays, and global costs of hospitalization, from 2010 to 2019. Temporal trend analysis and statistical comparisons were conducted to assess changes over time and differences between the treatment options. The mean annual number of aneurysm treatments with endovascular embolization was 2206.30 (± 309.5), with a non-significant increasing trend (B = 55.66; p = 0.104). Conversely, microsurgical clipping exhibited a significant decreasing trend (B = -69.97; p < 0.001) with a mean of 1133.1 (± 223.12) procedures. The mortality rate associated with clipping procedure was higher in the period, with a mean difference of 5.23 (± 0.39); ([CI95%: 4.36; 6.10]; p < 0.001) and showed an increase trend, while embolization showed a stable trend. The length of in-hospital stay remained stable for clipping but increased for embolization. Costs associated with clipping increased over time, whereas costs for embolization decreased. This study highlights a significant shift in the treatment of aneurysm towards Endovascular Embolization. Despite higher costs, endovascular procedures were associated with lower mortality rates and shorter hospital stays. These findings provide valuable insights into aneurysm treatment patterns and indicators in a middle-income country's Public Health System.


Subject(s)
Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Length of Stay , Surgical Instruments , Humans , Intracranial Aneurysm/surgery , Intracranial Aneurysm/therapy , Brazil , Embolization, Therapeutic/methods , Endovascular Procedures/trends , Endovascular Procedures/methods , Neurosurgical Procedures/trends , Aneurysm, Ruptured/surgery , Aneurysm, Ruptured/therapy , Male , Female , Middle Aged , Treatment Outcome , Microsurgery
7.
Orthod Craniofac Res ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715428

ABSTRACT

INTRODUCTION: An ideal orthodontic treatment involves qualitative and quantitative measurements of dental and skeletal components to evaluate patients' discrepancies, such as facial, occlusal, and functional characteristics. Deciding between orthodontics and orthognathic surgery remains challenging, especially in borderline patients. Advances in technology are aiding clinical decisions in orthodontics. The increasing availability of data and the era of big data enable the use of artificial intelligence to guide clinicians' diagnoses. This study aims to test the capacity of different machine learning (ML) models to predict whether orthognathic surgery or orthodontics treatment is required, using soft and hard tissue cephalometric values. METHODS: A total of 920 lateral radiographs from patients previously treated with either conventional orthodontics or in combination with orthognathic surgery were used, comprising n = 558 Class II and n = 362 Class III patients, respectively. Thirty-two measures were obtained from each cephalogram at the initial appointment. The subjects were randomly divided into training (n = 552), validation (n = 183), and test (n = 185) datasets, both as an entire sample and divided into Class II and Class III sub-groups. The extracted data were evaluated using 10 machine learning models and by a four-expert panel consisting of orthodontists (n = 2) and surgeons (n = 2). RESULTS: The combined prediction of 10 models showed top-ranked performance in the testing dataset for accuracy, F1-score, and AUC (entire sample: 0.707, 0.706, 0.791; Class II: 0.759, 0.758, 0.824; Class III: 0.822, 0.807, 0.89). CONCLUSIONS: The proposed combined 10 ML approach model accurately predicted the need for orthognathic surgery, showing better performance in Class III patients.

8.
Euro Surveill ; 29(18)2024 May.
Article in English | MEDLINE | ID: mdl-38699901

ABSTRACT

In March 2024, the first ever human case of rabies, following a dog bite, was detected in Timor-Leste. This paper briefly discusses the circumstances of transmission, clinical presentation, palliative care of the case and public health measures taken. Timor-Leste was previously considered rabies-free. Any person who is bitten or scratched by an animal that could potentially transmit rabies virus (especially dogs, bats, monkeys or cats) in Timor-Leste should be assessed for consideration of provision of rabies post-exposure prophylaxis.


Subject(s)
Bites and Stings , Post-Exposure Prophylaxis , Rabies virus , Rabies , Animals , Cats , Dogs , Female , Humans , Bites and Stings/virology , Chiroptera/virology , Rabies/diagnosis , Rabies/veterinary , Rabies/transmission , Rabies Vaccines/administration & dosage , Rabies virus/isolation & purification , Timor-Leste/epidemiology , Adolescent
9.
Int J Mol Sci ; 25(18)2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39337305

ABSTRACT

Graphene nanoplatelets (UGZ-1004) are emerging as a promising biomaterial in regenerative medicine. This study comprehensively evaluates UGZ-1004, focusing on its physical properties, cytotoxicity, intracellular interactions, and, notably, its effects on mesenchymal stem cells (MSCs). UGZ-1004 was characterized by lateral dimensions and layer counts consistent with ISO standards and demonstrated a high carbon purity of 0.08%. Cytotoxicity assessments revealed that UGZ-1004 is non-toxic to various cell lines, including 3T3 fibroblasts, VERO kidney epithelial cells, BV-2 microglia, and MSCs, in accordance with ISO 10993-5:2020/2023 guidelines. The study focused on MSCs and revealed that UGZ-1004 supports their gene expression alterations related to self-renewal and proliferation. MSCs exposed to UGZ-1004 maintained their characteristic surface markers. Importantly, UGZ-1004 promoted significant upregulation of genes crucial for cell cycle regulation and DNA repair, such as CDK1, CDK2, and MDM2. This gene expression profile suggests that UGZ-1004 can enhance MSC self-renewal capabilities, ensuring robust cellular function and longevity. Moreover, UGZ-1004 exposure led to the downregulation of genes associated with tumor development, including CCND1 and TFDP1, mitigating potential tumorigenic risks. These findings underscore the potential of UGZ-1004 to not only bolster MSC proliferation but also enhance their self-renewal processes, which are critical for effective regenerative therapies. The study highlights the need for continued research into the long-term impacts of graphene nanoplatelets and their application in MSC-based regenerative medicine.


Subject(s)
Cell Proliferation , Graphite , Mesenchymal Stem Cells , Cell Proliferation/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Animals , Graphite/chemistry , Graphite/pharmacology , Mice , Chlorocebus aethiops , Cell Self Renewal/drug effects , Cell Self Renewal/genetics , Vero Cells , Gene Expression Regulation/drug effects , Nanoparticles/chemistry , Cell Line , Nanostructures/chemistry
10.
Int J Mol Sci ; 25(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39126055

ABSTRACT

Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.


Subject(s)
Encephalitis , Humans , Encephalitis/genetics , Encephalitis/pathology , Encephalitis/metabolism , Male , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Brain/pathology , Brain/metabolism , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/pathology , Cerebral Cortex/metabolism , Female , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Cell Cycle/genetics
11.
Int J Mol Sci ; 25(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39000479

ABSTRACT

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps to identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. In addition, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, the analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.


Subject(s)
Biomarkers , Central Nervous System Diseases , Extracellular Vesicles , Humans , Extracellular Vesicles/metabolism , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/therapy , Central Nervous System Diseases/diagnosis , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Mesenchymal Stem Cells/metabolism , Neurodegenerative Diseases/therapy , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/diagnosis
12.
Int J Mol Sci ; 25(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39062991

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention strategies. We conducted a cohort study comprising 43 elderly COVID-19 patients admitted to São Lucas Hospital, PUCRS, Brazil. Anthropometric measurements, including calf circumference (CC) and abdominal circumference (AC), were assessed alongside molecular analyses of peripheral blood samples obtained within 48 h of hospital admission. Sociodemographic data were collected from electronic medical records for comprehensive analysis. Our findings revealed a possible relationship between overweight status, increased abdominal adiposity, and prolonged hospitalization duration, alongside heightened disease severity. We also found no significant correlations between BMI, vitamin D levels, and clinical outcomes. Elevated oxygen requirements were observed in both normal and overweight individuals, with the latter necessitating prolonged oxygen therapy. Molecular analyses revealed changes in the inflammatory profile regarding the outcome of the patients. Our study highlights the critical importance of both anthropometric and molecular markers in predicting disease severity and clinical outcomes in elderly individuals with COVID-19.


Subject(s)
Biomarkers , COVID-19 , SARS-CoV-2 , Humans , COVID-19/blood , Aged , Male , Female , Biomarkers/blood , Aged, 80 and over , Severity of Illness Index , Inflammation/blood , Nutritional Status , Brazil/epidemiology , Cohort Studies , Body Mass Index , Overweight/blood
13.
Am J Orthod Dentofacial Orthop ; 165(3): 321-331, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38010236

ABSTRACT

INTRODUCTION: Skeletal stability after bimaxillary surgical correction of Class III malocclusion was investigated through a qualitative and quantitative analysis of the maxilla and the distal and proximal mandibular segments using a 3-dimensional voxel-based superimposition among virtual surgical predictions performed by the orthodontist in close communication with the maxillofacial surgeon and 12-18 months postoperative outcomes. METHODS: A comprehensive secondary data analysis was conducted on deidentified preoperative (1 month before surgery [T1]) and 12-18 months postoperative (midterm [T2]) cone-beam computed tomography scans, along with virtual surgical planning (VSP) data obtained by Dolphin Imaging software. The sample for the study consisted of 17 patients (mean age, 24.8 ± 3.5 years). Using 3D Slicer software, automated tools based on deep-learning approaches were used for cone-beam computed tomography orientation, registration, bone segmentation, and landmark identification. Colormaps were generated for qualitative analysis, whereas linear and angular differences between the planned (T1-VSP) and observed (T1-T2) outcomes were calculated for quantitative assessments. Statistical analysis was conducted with a significance level of α = 0.05. RESULTS: The midterm surgical outcomes revealed a slight but significantly less maxillary advancement compared with the planned position (mean difference, 1.84 ± 1.50 mm; P = 0.004). The repositioning of the mandibular distal segment was stable, with insignificant differences in linear (T1-VSP, 1.01 ± 3.66 mm; T1-T2, 0.32 ± 4.17 mm) and angular (T1-VSP, 1.53° ± 1.60°; T1-T2, 1.54° ± 1.50°) displacements (P >0.05). The proximal segments exhibited lateral displacement within 1.5° for both the mandibular right and left ramus at T1-VSP and T1-T2 (P >0.05). CONCLUSIONS: The analysis of fully digital planned and surgically repositioned maxilla and mandible revealed excellent precision. In the midterm surgical outcomes of maxillary advancement, a minor deviation from the planned anterior movement was observed.


Subject(s)
Malocclusion, Angle Class III , Orthognathic Surgical Procedures , Humans , Young Adult , Adult , Orthognathic Surgical Procedures/methods , Malocclusion, Angle Class III/diagnostic imaging , Malocclusion, Angle Class III/surgery , Orthodontists , Imaging, Three-Dimensional , Mandible/diagnostic imaging , Mandible/surgery , Cone-Beam Computed Tomography , Maxilla/diagnostic imaging , Maxilla/surgery , Cephalometry
14.
Rev Esp Enferm Dig ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39364729

ABSTRACT

A 78-year-old male presented to the emergency department with melena. He was hemodynamically stable but displayed a hemoglobin level of 5.8g/dL necessitating blood transfusion. Initial esophagogastroduodenoscopy and colonoscopy failed to identify a bleeding source, prompting a capsule endoscopy that revealed an active bleeding site in the jejunum. A single-balloon enteroscopy identified an aberrant vessel in the mid-jejunum protruding through a 3mm mucosal defect, devoid of surrounding inflammation, consistent with a Dieulafoy's lesion, in which two through-the-scope clips were applied. Despite this, ongoing melena and decreasing hemoglobin levels in the subsequent days led to a second single-balloon enteroscopy, which confirmed continued bleeding. Definitive hemostasis was achieved through diluted adrenaline injection, four additional through-the-scope clips, and polidocanol sclerotherapy. Jejunal Dieulafoy's lesion is extremely rare and presents notable diagnostic and therapeutic challenges. Ávila et al. recently reported a case where, despite capsule endoscopy identifying the bleeding site, single-balloon enteroscopy failed to confirm the diagnosis, leading to the use of motorized enteroscopy with argon and metallic clip treatment. Similarly, our experience highlights the diagnostic value of capsule endoscopy and the crucial role of device-assisted enteroscopy in a multimodal therapeutic approach, which was essential for achieving successful hemostasis.

15.
Gastroenterol Hepatol ; : 502235, 2024 Aug 05.
Article in English, Spanish | MEDLINE | ID: mdl-39111390

ABSTRACT

OBJECTIVE: Crohn's disease (CD) is heterogeneous, and proximal involvement in the small bowel (SB) is associated with worse outcomes. Nonetheless, studies on the impact of duodenal and jejunal lesions in SB CD are limited. This study aimed to investigate the clinical characteristics and outcomes of individuals diagnosed with SB CD, comparing those with and without proximal inflammation. METHODS: A cohort of 53 treatment-naive SB CD patients that underwent Capsule Endoscopy at diagnosis were retrospectively selected. The inflammatory activity was quantified using the Lewis Score for each SB tertile. RESULTS: Thirty-seven (69.8%) patients displayed inflammatory activity in the first and/or second tertile together with third tertile involvement (Proximal+T3 group). Sixteen (30.2%) had inflammation in the third tertile only (T3 group). Individuals in the Proximal+T3 group had a higher risk for moderate-to-severe inflammation (OR 4.93, 95% CI: 1.3-18.3, p=0.013). A subgroup analysis for those with mild inflammatory activity showed that individuals in the Proximal+T3 group initiated biologic drugs more often (OR 11, 95% CI: 1.1-109.7, p=0.036). CONCLUSION: Proximal SB lesions are associated with increased inflammatory activity, necessitating more frequent use of biologics in patients with mild disease. Early detection of proximal SB CD with Capsule Endoscopy may contribute to timely treatment.

16.
EMBO J ; 38(14): e101109, 2019 07 15.
Article in English | MEDLINE | ID: mdl-31304627

ABSTRACT

Centriolar satellites are small electron-dense granules that cluster in the vicinity of centrosomes. Satellites have been implicated in multiple critical cellular functions including centriole duplication, centrosome maturation, and ciliogenesis, but their precise composition and assembly properties have remained poorly explored. Here, we perform in vivo proximity-dependent biotin identification (BioID) on 22 human satellite proteins, to identify 2,113 high-confidence interactions among 660 unique polypeptides. Mining this network, we validate six additional satellite components. Analysis of the satellite interactome, combined with subdiffraction imaging, reveals the existence of multiple unique microscopically resolvable satellite populations that display distinct protein interaction profiles. We further show that loss of satellites in PCM1-depleted cells results in a dramatic change in the satellite interaction landscape. Finally, we demonstrate that satellite composition is largely unaffected by centriole depletion or disruption of microtubules, indicating that satellite assembly is centrosome-independent. Together, our work offers the first systematic spatial and proteomic profiling of human centriolar satellites and paves the way for future studies aimed at better understanding the biogenesis and function(s) of these enigmatic structures.


Subject(s)
Autoantigens/genetics , Cell Cycle Proteins/genetics , Centrioles/metabolism , Proteomics/methods , Autoantigens/metabolism , Cell Cycle Proteins/metabolism , Cell Line , Gene Deletion , Humans , Microtubule-Associated Proteins/metabolism , Protein Interaction Maps , Tandem Mass Spectrometry
17.
Am J Hum Genet ; 107(2): 342-351, 2020 08 06.
Article in English | MEDLINE | ID: mdl-32673564

ABSTRACT

Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.


Subject(s)
Cell Cycle Checkpoints/genetics , Infertility, Male/genetics , Meiosis/genetics , Mutation/genetics , Proteins/genetics , Spermatogenesis/genetics , Adult , Alleles , Animals , Azoospermia/genetics , Homozygote , Humans , Male , Mice , Phenotype , Spermatozoa/abnormalities , Testis/abnormalities , Turkey , Exome Sequencing/methods
18.
Sensors (Basel) ; 23(17)2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37687849

ABSTRACT

In maritime settings, effective communication between vessels and land infrastructure is crucial, but existing technologies often prove impractical for energy-sensitive IoT applications, like deploying sensors at sea. In this study, we explore the viability of a low-power, cost-effective wireless communication solution for maritime sensing data. Specifically, we conduct an experimental assessment of the Azorean Long Range Wide Area Network (LoRaWAN) coverage. Our tests involve positioning the gateway at the island's highest point and installing end nodes on medium-sized fishing vessels. Through measurements of received signal strength indicator (RSSI), signal-to-noise ratio (SNR), and lines of sight (LOS), we showcase the potential of LoRaWAN transmissions to achieve communication distances exceeding 130 km in a LOS-free scenario over the ocean. These findings highlight the promising capabilities of LoRaWAN for reliable and long-range maritime communication of sensing data.

19.
Molecules ; 28(14)2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37513198

ABSTRACT

This paper demonstrates the generation of broadband emission in the visible and infrared ranges induced by a concentrated beam of infrared radiation from CsPbBr3 ceramics doped with Yb3+ ions. The sample was obtained by the conventional solid-state reaction method, and XRD measurements confirmed the phase purity of the material crystallizing in the orthorhombic system. Spectroscopic measurements required further sample preparation in the form of ceramics using a high-pressure press. The research showed that as the excitation power increases, the emission intensity does not increase linearly from the beginning of the experiment. Irradiation of the material results in the accumulation of the delivered energy. Absorption of a sufficient number of photons triggers avalanche emission. It was found that the most intense luminescence is produced in a vacuum. Changes in conductivity were also observed, where the excitation was able to lower the resistivity of the material and it was highly dependent on the excitation power. The mechanism responsible for the generation of the observed phenomenon involving intervalence charge transfer (IVCT) transitions has been postulated.

20.
Molecules ; 28(21)2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37959787

ABSTRACT

BACKGROUND: Grape agri-food wastes, such as skin, seeds, and other discarded by-products, contain phytochemical compounds that offer potential health benefits. METHODS: This study aimed to investigate the polyphenol composition and bioactivities of different extracts obtained from grape marc and seeds, with the goal of exploring their potential for application as natural food additives. RESULTS: Regardless of the extraction method used (dynamic maceration, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)), all extracts exhibited relatively high concentrations of phenolic compounds. The chemical characterization of the extracts revealed the presence of specific compounds and chemical groups associated with each extraction methodology. Moreover, the extracts displayed satisfactory antioxidant activities, especially in inhibiting lipoperoxidation as assessed by the TBARS assay. Additionally, the extracts demonstrated effective inhibition against different strains of bacteria and fungi known as food contaminants. Taken together, these findings indicate that those extracts have the potential to be tested as natural antioxidants and preservatives with sustainable origins in food and beverage systems. Among the extraction methods evaluated, traditional maceration and UAE provided extracts with the highest antioxidant and antimicrobial activities. CONCLUSIONS: Our results suggest the opportunity to explore grape marc and seeds discarded by the winery industry in Portugal as natural sources of bioactive compounds, which could be employed as functional food ingredients or technological additives. The valorization of grape biowastes offers a promising strategy to reduce waste and harness their potential health benefits.


Subject(s)
Refuse Disposal , Vitis , Polyphenols/chemistry , Vitis/chemistry , Antioxidants/chemistry , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Plant Extracts/chemistry , Seeds/chemistry
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