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1.
JSES Int ; 8(4): 873-879, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035641

RESUMO

Background: Peripheral nerve injury is a recognized complication after reverse shoulder arthroplasty (RSA) that has mainly been studied at the level of the brachial plexus and its proximal branches. However, the impact of RSA on distal peripheral nerves and the influence of elbow and wrist position is not known. This cadaveric study aimed to analyze the effect of RSA implantation and upper limb position on tension in the distal median and radial nerves. The hypothesis was that RSA increased distal nerve tension, which could be further affected by elbow and wrist position. Methods: 12 upper limbs in 9 full fresh-frozen cadavers were dissected. Nerve tension was measured in the median nerve at the level of the proximal arm, elbow, and distal forearm, and in the radial nerve at the level of the elbow, using a customized three-point tensiometer. Measurements were carried out before and after RSA implantation, using a semi-inlay implant (Medacta, Castel San Pietro, Switzerland). Two different configurations were tested, using the smallest and largest available implant sizes. Three upper-limb key positions were considered (plexus at risk, plexus relief, and neutral), from which the effect of elbow and wrist position was further tested. Results: RSA implantation significantly increased median and radial nerve tension throughout the upper limb. The distal nerve segments were particularly dependent on elbow and wrist position. The plexus at risk position induced the most tension in all nerve segments, especially with the large implant configuration. On the other hand, the plexus relief position induced the least amount of tension. Flexing the elbow was the most efficient way to decrease nerve tension in all tested nerve segments and key positions. Wrist flexion significantly decreased nerve tension in the median nerve, whereas wrist extension decreased tension in the radial nerve. Conclusion: RSA significantly increases tension in the median and radial nerves and makes them more susceptible to wrist and elbow positioning. The mechanism behind distal peripheral neuropathy after RSA may thus result from increased compression of tensioned nerves against anatomical fulcrums rather than nerve elongation alone. Elbow flexion was the most effective way to decrease nerve tension, while elbow extension should be avoided when implanting the humeral component. Further studies are needed to assess the ulnar nerve.

2.
Eur Radiol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856779

RESUMO

OBJECTIVES: To determine prevalence in the symptomatic population of dorsal mucoid cysts centered on dorsal capsuloscapholunate septum (DCSS) using high-field magnetic resonance imaging (MRI) for anatomoclinical and epidemiological correlations. MATERIALS AND METHODS: This single-center retrospective study analyzed all 3-Tesla MRIs consecutively performed for painful wrists in 295 patients. Two blinded readers performed measurements. The protocol included T1 spin echo and 3D proton density sequences with fat saturation. Inter-observer reliability was assessed using kappa and intra-class correlation coefficients for cyst detection and volumetry, respectively. Disagreements concerning cyst detection were resolved by a consensus reading. Cyst size, relationship to extrinsic and scapholunate ligaments (SL), continuity of SL, minimum distance to the posterior interosseous nerve (PIN), cyst communication with joint, and anatomical classifications of cysts were analyzed. Correlation tests were performed to assess associations. RESULTS: Two-hundred ninety-five patients (mean age 39.6 +/- 15.6 (standard deviation), 161 males) were evaluated for detection of dorsal wrist cysts identified in 150/295. In this subgroup, the mean age was 38.7 years (15-75), the sex ratio of 0.6 (59% women), and the median volume cyst of 8.7 mm3 (0.52-2555). Cyst detection, volume, and major axis measurements showed very high agreement between observers, respectively, 0.89, 0.96, and 0.91. 42 patients had dorsal SL pain. A weak negative correlation was found between distance to PIN and dorsal SL pain (r = -0.2415; p < 0.05) and a weak positive correlation between Guérini's classification and dorsal SL pain (r = 0.2466; p < 0.05). CONCLUSION: High-field MRI is the modality of choice for the detection, anatomical, and volumetric assessment of dorsal cysts. Preoperative assessment will be aided by the proposed revised anatomical classification. CLINICAL RELEVANCE STATEMENT: High-field MRI is the modality of choice for the anatomical study of dorsal ganglion cysts. It allows the radiologist to accurately describe the anatomical relationships, size, and visibility of the pedicle, essential information for the surgeon's preoperative assessment. KEY POINTS: Dorsal mucoid wrist ganglion is a condition for which prevalence remains to be determined. High-field MRI is a reproducible imaging modality for the detection and assessment of dorsal wrist cysts. High-field MRI has a key role in the preoperative management of dorsal mucoid cysts.

3.
Eur J Radiol ; 177: 111561, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897054

RESUMO

INTRODUCTION: The trapeziometacarpal (TMC) joint is a complex joint, whose anatomy and function are different from the metacarpophalangeal joints of the long fingers. The stability of this joint is ensured at three levels by multiple structures: osteochondral, capsulo-ligamentous, and musculo-tendinous. The anatomical and biomechanical structures ensuring the stability of the TMC joint are perfectly evaluated on magnetic resonance imaging (MRI), with a high degree of confidence. All described ligaments are anatomically visible and perfectly assessed on MRI and ultrasound (US): the dorsoradial ligament, the posterior oblique ligament, the intermetacarpal ligament, the ulnar collateral ligament, the two bundles of the anterior oblique ligament (break ligament), as well as the superficial anterior oblique and deep anterior oblique ligaments. METHODOLOGY: This educational review assesses the TMC joint anatomy using high-field MRI and US compared with cadaveric specimens as well the biomechanics of this joint. In addition, it highlights pathological patterns of traumatic (sprain, dislocation, and fractures) and degenerative diseases. RESULTS AND CONCLUSION: Knowledge of TMC joint anatomy is crucial to the radiologists' understanding and assessment of various traumatic and degenerative pathologies, and thus helps clinicians and surgeons choose the appropriate treatment.


Assuntos
Cadáver , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Ultrassonografia , Humanos , Imageamento por Ressonância Magnética/métodos , Ultrassonografia/métodos , Tomografia Computadorizada por Raios X/métodos , Articulações Carpometacarpais/diagnóstico por imagem
4.
Handchir Mikrochir Plast Chir ; 56(3): 201-211, 2024 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-38861975

RESUMO

The introduction of the new generation of thumb carpometacarpal (CMC I) joint implants for the treatment of CMC I osteoarthritis has significantly broadened the scope of hand surgery in recent years. However, the technical demands of the procedure and the many details that need to be considered require appropriate training and a learning curve. To share experiences with the Touch CMC I prosthesis, we held the first German-speaking CMC I joint prosthetics user meeting in Zurich. After some basic introductory lectures on biomechanics and the principles of prosthetic fitting of the CMC I joint, the various challenges associated with CMC I joint prosthetics were discussed in interactive expert panels. Subsequently, cases were discussed in small groups under expert guidance and the respective conclusions were discussed in plenary. The main results of this symposium are summarised in this manuscript.


Assuntos
Articulações Carpometacarpais , Prótese Articular , Osteoartrite , Desenho de Prótese , Polegar , Humanos , Masculino , Fenômenos Biomecânicos , Articulações Carpometacarpais/cirurgia , Osteoartrite/cirurgia , Ajuste de Prótese , Polegar/cirurgia
5.
J Extracell Biol ; 3(1): e128, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38938674

RESUMO

Human milk extracellular vesicles (HM EVs) are proposed to protect against disease development in infants. This protection could in part be facilitated by the bioactive EV cargo of proteins and RNA. Notably, mothers birth infants of different gestational ages with unique needs, wherein the EV cargo of HM may diverge. We collected HM from lactating mothers within two weeks of a term or preterm birth. Following purification of EVs, proteins and mRNA were extracted for proteomics and sequencing analyses, respectively. Over 2000 protein groups were identified, and over 8000 genes were quantified. The total number of proteins and mRNA did not differ significantly between the two conditions, while functional bioinformatics of differentially expressed cargo indicated enrichment in immunoregulatory cargo for preterm HM EVs. In term HM EVs, significantly upregulated cargo was enriched in metabolism-related functions. Based on gene expression signatures from HM-contained single cell sequencing data, we proposed that a larger portion of preterm HM EVs are secreted by immune cells, whereas term HM EVs contain more signatures of lactocyte epithelial cells. Proposed differences in EV cargo could indicate variation in mother's milk based on infants' gestational age and provide basis for further functional characterisation.

6.
J Neurosci ; 44(29)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38744530

RESUMO

Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class selective melatonin MT1 receptor partial agonist UCM871 increases the duration of REMS without affecting that of NREMS. The REMS-promoting effects of UCM871 occurred by inhibiting, in a dose-response manner, the firing activity of the locus ceruleus (LC) norepinephrine (NE) neurons, which express MT1 receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT1 pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT1 receptors in the LC-NE neurons. In conclusion, MT1 receptor agonism inhibits LC-NE neurons and triggers REMS, thus representing a novel mechanism and target for REMS disorders and/or psychiatric disorders associated with REMS impairments.


Assuntos
Locus Cerúleo , Ratos Sprague-Dawley , Receptor MT1 de Melatonina , Sono REM , Animais , Masculino , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/metabolismo , Locus Cerúleo/fisiologia , Ratos , Receptor MT1 de Melatonina/agonistas , Receptor MT1 de Melatonina/metabolismo , Sono REM/fisiologia , Sono REM/efeitos dos fármacos , Norepinefrina/metabolismo , Neurônios Adrenérgicos/efeitos dos fármacos , Neurônios Adrenérgicos/metabolismo , Neurônios Adrenérgicos/fisiologia , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/fisiologia
7.
Biomol Biomed ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38606907

RESUMO

The 67 kDa laminin receptor (67LR) was identified as the first laminin receptor shown to be involved in the carcinogenesis of various cancers, including colorectal cancer. While the exact composition of this 67 kDa receptor remains unknown, it has been reported to be formed by the 37 kDa ribosomal protein SA (RPSA) covalently attached to another unidentified protein. Our analysis of 67LR in colorectal cancer cell extracts showed the 67 kDa immunoreactive protein corresponding to 67LR in the soluble protein fraction, while some 37 kDa RPSA exhibited plasma membrane-like properties. Proteomic analysis of the 67 kDa fraction revealed the absence of RPSA, however, the ß-galactosidase-related 67 kDa elastin-binding protein, another laminin binding receptor, was identified. The downregulation of ß-galactosidase through short hairpin RNA (shRNA) led to a reduction in both 67LR and 67EBP immunoreactive proteins, indicating a possible misidentification of 67LR and 67EBP in colorectal cancer cells.

10.
Biomedicines ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38397935

RESUMO

Inflammatory bowel disease (IBD) flare-ups exhibit symptoms that are similar to other diseases and conditions, making diagnosis and treatment complicated. Currently, the gold standard for diagnosing and monitoring IBD is colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method. In this study, our aim was to provide proof of concept for the application of Sequential Window Acquisition of All Theoretical Mass Spectra-Mass spectrometry (SWATH-MS) and machine learning to develop a non-invasive and accurate predictive model using the stool proteome to distinguish between active IBD patients and symptomatic non-IBD patients. Proteome profiles of 123 samples were obtained and data processing procedures were optimized to select an appropriate pipeline. The differentially abundant analysis identified 48 proteins. Utilizing correlation-based feature selection (Cfs), 7 proteins were selected for proceeding steps. To identify the most appropriate predictive machine learning model, five of the most popular methods, including support vector machines (SVMs), random forests, logistic regression, naive Bayes, and k-nearest neighbors (KNN), were assessed. The generated model was validated by implementing the algorithm on 45 prospective unseen datasets; the results showed a sensitivity of 96% and a specificity of 76%, indicating its performance. In conclusion, this study illustrates the effectiveness of utilizing the stool proteome obtained through SWATH-MS in accurately diagnosing active IBD via a machine learning model.

11.
J Anat ; 244(4): 620-627, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38214341

RESUMO

Imaging techniques in anatomy have developed rapidly over the last decades through the emergence of various 3D scanning systems. Depending on the dissection level, non-contact or tactile contact methods can be applied on the targeted structure. The aim of this study was to assess the inter and intra-observer reproducibility of an ArUco-based localisation stylus, that is, a manual technique on a hand-held stylus. Ten fresh-frozen, unembalmed adult arms were used to digitalise the glenoid cartilage related to the glenohumeral joint and the contour of the clavicle cartilage related to the acromioclavicular joint. Three operators performed consecutive digitalisations of each cartilage contour using an ArUco-based localisation stylus recorded by a single monocular camera. The shape of each cartilage was defined by nine shape parameters. Intra-observer repeatability and inter-observer reproducibility were computed using an intra-class correlation (ICC) for each of these parameters. Overall, 35.2 ± 2.4 s and 26.6 ± 10.2 s were required by each examiner to digitalise the contour of a glenoid and acromioclavicular cartilage, respectively. For most parameters, good-to-excellent agreements were observed concerning intra-observer (ICC ranging between 0.81 and 1.00) and inter-observer (ICC ranging between 0.75 and 0.99) reproducibility. To conclude, through a fast and versatile process, the use of an ArUco-based localisation stylus can be a reliable low-cost alternative to conventional imaging methods to digitalise shoulder cartilage contours.


Assuntos
Articulação do Ombro , Ombro , Adulto , Humanos , Reprodutibilidade dos Testes , Variações Dependentes do Observador , Cartilagem
12.
Artigo em Inglês | MEDLINE | ID: mdl-38000716

RESUMO

BACKGROUND: miR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing. METHODS: Using RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). RESULTS: In 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. CONCLUSIONS: The functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.


Assuntos
MicroRNAs , Esquizofrenia , Humanos , Estudo de Associação Genômica Ampla , Encéfalo , MicroRNAs/genética , MicroRNAs/metabolismo , Emoções
13.
Br J Pharmacol ; 180 Suppl 2: S23-S144, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123151

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Receptores Acoplados a Proteínas G , Humanos , Ligantes , Canais Iônicos/química , Receptores Citoplasmáticos e Nucleares
14.
Int J Mol Sci ; 24(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685847

RESUMO

Metallic nanoparticles (mNPs) are widely used as food additives and can interact with gliadin triggering an immune response, but evaluation of the effects on crypts, hypertrophic in celiac subjects, is still lacking. This study evaluated the effects of gold and silver mNPs in combination with gliadin on crypt-like cells (HIEC-6). Transmission electron microscopy (TEM) was used to evaluate gliadin-mNP aggregates in cells. Western blot and immunofluorescence analysis assessed autophagy-related molecule levels (p62, LC3, beclin-1, EGFR). Lysosome functionality was tested with acridine orange (AO) and Magic Red assays. TEM identified an increase in autophagic vacuoles after exposure to gliadin + mNPs, as also detected by significant increments in LC3-II and p62 expression. Immunofluorescence confirmed the presence of mature autophagosomes, showing LC3 and p62 colocalization, indicating an altered autophagic flux, further assessed with EGFR degradation, AO and Magic Red assays. The results showed a significant reduction in lysosomal enzyme activity and a modest reduction in acidity. Thus, gliadin + mNPs can block the autophagic flux inducing a lysosomal defect. The alteration of this pathway, essential for cell function, can lead to cell damage and death. The potential effects of this copresence in food should be further characterized to avoid a negative impact on celiac disease subjects.


Assuntos
Ouro , Nanopartículas , Humanos , Glutens , Prata , Gliadina , Autofagia , Laranja de Acridina , Receptores ErbB
15.
J Lipid Res ; 64(9): 100423, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558128

RESUMO

Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD. The present study was conducted to better understand little-known aspects of Sar1b mutations, including mouse embryonic development, lipid profile, and lipoprotein composition in response to high-fat diet, gut and liver cholesterol metabolism, sex-specific effects, and genotype-phenotype differences. Sar1b deletion and mutation produce a lethal phenotype in homozygous mice, which display intestinal lipid accumulation without any gross morphological abnormalities. On high-fat diet, mutant mice exhibit more marked abnormalities in body composition, adipose tissue and liver weight, plasma cholesterol, non-HDL cholesterol and polyunsaturated fatty acids than those on the regular Chow diet. Divergences were also noted in lipoprotein lipid composition, lipid ratios (serving as indices of particle size) and lipoprotein-apolipoprotein distribution. Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. Noteworthy, variations were observed between males and females, and between Sar1b deletion and mutation phenotypes. Overall, mutant animal findings reveal the importance of Sar1b in several biochemical, metabolic and developmental processes.


Assuntos
Dieta Hiperlipídica , Desenvolvimento Embrionário , Proteínas Monoméricas de Ligação ao GTP , Animais , Feminino , Humanos , Masculino , Camundongos , Colesterol/metabolismo , Quilomícrons/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética
16.
Exp Cell Res ; 430(2): 113723, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37499931

RESUMO

Intestinal epithelial cell differentiation is a highly controlled and orderly process occurring in the crypt so that cells migrating out to cover the villi are already fully functional. Absorptive cell precursors, which originate from the stem cell population located in the lower third of the crypt, are subject to several cycles of amplification in the transit amplifying (TA) zone, before reaching the terminal differentiation compartment located in the upper third. There is a large body of evidence that absorptive cell differentiation is halted in the TA zone through various epigenetic, transcriptional and intracellular signalling events or mechanisms allowing the transient expansion of this cell population but how these mechanisms are themself regulated remains obscure. One clue can be found in the epithelial cell-matrix microenvironment located all along the crypt-villus axis. Indeed, a previous study from our group revealed that α5-subunit containing laminins such as lamimin-511 and 512 inhibit early stages of differentiation in Caco-2/15 cells. Among potential receptors for laminin 511/512 is the integrin α7ß1, which has previously been reported to be expressed in the human intestinal crypts and in early stages of Caco-2/15 cell differentiation. In this study, the effects of knocking down ITGA7 in Caco-2/15 cells were studied using shRNA and CRISPR/Cas9 strategies. Abolition of the α7 integrin subunit resulted in a significant increase in the level of differentiation and polarization markers as well as the morphological features of intestinal cells. Activities of focal adhesion kinase and Src kinase were both reduced in α7-knockdown cells while the three major intestinal pro-differentiation factors CDX2, HNFα1 and HNF4α were overexpressed. Two epigenetic events associated with intestinal differentiation, the reduction of tri-methylated lysine 27 on histone H3 and the increase of acetylation of histone H4 were also observed in α7-knockdown cells. On the other hand, the ablation of α7 had no effect on cell proliferation. In conclusion, these data indicate that integrin α7ß1 acts as a major repressor of absorptive cell terminal differentiation in the Caco-2/15 cell model and suggest that the laminin-α7ß1 integrin interaction occurring in the transit amplifying zone of the adult intestine is involved in the transient halting of absorptive cell terminal differentiation.


Assuntos
Integrinas , Intestinos , Humanos , Células CACO-2 , Integrinas/genética , Integrinas/metabolismo , Diferenciação Celular/fisiologia , Histonas/metabolismo
17.
Hippocampus ; 33(10): 1075-1093, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37421207

RESUMO

We investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule ß-arrestin-2 (ß-Arr2) is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and survival of adult-born granule cells are absent in the ß-Arr2 knockout (KO) mice. To our surprise, fluoxetine induced a dramatic upregulation of the number of doublecortin (DCX)-expressing cells in the ß-Arr2 KO mice, indicating that this marker can be increased even though AHN is not. We discovered two other conditions where a complex relationship occurs between the number of DCX-expressing cells compared to levels of AHN: a chronic antidepressant model where DCX is upregulated and an inflammation model where DCX is downregulated. We concluded that assessing the number of DCX-expressing cells alone to quantify levels of AHN can be complex and that caution should be applied when label retention techniques are unavailable.


Assuntos
Proteína Duplacortina , Fluoxetina , Animais , Camundongos , Antidepressivos/farmacologia , Fluoxetina/farmacologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Neurônios
18.
Cells ; 12(7)2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37048132

RESUMO

Primary cilia are sensory antennae located at the cell surface which mediate a variety of extracellular signals involved in development, tissue homeostasis, stem cells and cancer. Primary cilia are found in an extensive array of vertebrae cells but can only be generated when cells become quiescent. The small intestinal epithelium is a rapidly self-renewing tissue organized into a functional unit called the crypt-villus axis, containing progenitor and differentiated cells, respectively. Terminally differentiated villus cells are notoriously devoid of primary cilia. We sought to determine if intestinal crypts contain a quiescent cell population that could be identified by the presence of primary cilia. Here we show that primary cilia are detected in a subset of cells located deep in the crypts slightly above a Paneth cell population. Using a normal epithelial proliferative crypt cell model, we show that primary cilia assembly and activity correlate with a quiescent state. These results provide further evidence for the existence of a quiescent cell population in the human small intestine and suggest the potential for new modes of regulation in stem cell dynamics.


Assuntos
Cílios , Intestino Delgado , Humanos , Duodeno , Divisão Celular , Celulas de Paneth
19.
Front Plant Sci ; 14: 1137834, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035077

RESUMO

Introduction: Genomic selection is becoming a standard technique in plant breeding and is now being introduced into forest tree breeding. Despite promising results to predict the genetic merit of superior material based on their additive breeding values, many studies and operational programs still neglect non-additive effects and their potential for enhancing genetic gains. Methods: Using two large comprehensive datasets totaling 4,066 trees from 146 full-sib families of white spruce (Picea glauca (Moench) Voss), we evaluated the effect of the inclusion of dominance on the precision of genetic parameter estimates and on the accuracy of conventional pedigree-based (ABLUP-AD) and genomic-based (GBLUP-AD) models. Results: While wood quality traits were mostly additively inherited, considerable non-additive effects and lower heritabilities were detected for growth traits. For growth, GBLUP-AD better partitioned the additive and dominance effects into roughly equal variances, while ABLUP-AD strongly overestimated dominance. The predictive abilities of breeding and total genetic value estimates were similar between ABLUP-AD and GBLUP-AD when predicting individuals from the same families as those included in the training dataset. However, GBLUP-AD outperformed ABLUP-AD when predicting for new unphenotyped families that were not represented in the training dataset, with, on average, 22% and 53% higher predictive ability of breeding and genetic values, respectively. Resampling simulations showed that GBLUP-AD required smaller sample sizes than ABLUP-AD to produce precise estimates of genetic variances and accurate predictions of genetic values. Still, regardless of the method used, large training datasets were needed to estimate additive and non-additive genetic variances precisely. Discussion: This study highlights the different quantitative genetic architectures between growth and wood traits. Furthermore, the usefulness of genomic additive-dominance models for predicting new families should allow practicing mating allocation to maximize the total genetic values for the propagation of elite material.

20.
Hand Surg Rehabil ; 42(3): 236-242, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37105520

RESUMO

OBJECTIVES: If symptoms recur after primary neurolysis of the median nerve, surgical revision is required. Soltani et al. (2013) demonstrated that surgical revision with vascularized flap coverage had a higher success rate (86%) than surgical revision without a flap (75%). The aim of this retrospective study was to present clinical outcomes in 36 cases of secondary open neurolysis of the median nerve, with synovial flap in case of recurrent carpal tunnel syndrome. METHOD: Thirty-three patients (36 hands) who had undergone secondary neurolysis of the median nerve combined with synovial flap coverage between 2012 and 2019 were selected for this study. We included only recurrent carpal tunnel syndrome cases presenting with scarring of the transverse carpal ligament or epineural fibrosis of the median nerve and with a symptom-free period of at least 3 months. The results were ranked on a 4-point scale as excellent, good, null or poor, depending on progression at last follow-up. RESULTS: Descriptive analysis showed that 80% of patients had a positive outcome (excellent 33%, good 47%), 6% null outcome and 14% poor outcome. CONCLUSION: This is an interesting, relatively non-invasive surgical option, and should be part of the therapeutic armamentarium for recurrent carpal tunnel syndrome in case of adherence of the nerve to the transverse carpal ligament.


Assuntos
Síndrome do Túnel Carpal , Humanos , Síndrome do Túnel Carpal/cirurgia , Estudos Retrospectivos , Nervo Mediano/cirurgia , Reoperação , Procedimentos Neurocirúrgicos
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