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1.
Psychol Assess ; 36(6-7): 395-406, 2024.
Article in English | MEDLINE | ID: mdl-38829349

ABSTRACT

This article illustrates novel quantitative methods to estimate classification consistency in machine learning models used for screening measures. Screening measures are used in psychology and medicine to classify individuals into diagnostic classifications. In addition to achieving high accuracy, it is ideal for the screening process to have high classification consistency, which means that respondents would be classified into the same group every time if the assessment was repeated. Although machine learning models are increasingly being used to predict a screening classification based on individual item responses, methods to describe the classification consistency of machine learning models have not yet been developed. This article addresses this gap by describing methods to estimate classification inconsistency in machine learning models arising from two different sources: sampling error during model fitting and measurement error in the item responses. These methods use data resampling techniques such as the bootstrap and Monte Carlo sampling. These methods are illustrated using three empirical examples predicting a health condition/diagnosis from item responses. R code is provided to facilitate the implementation of the methods. This article highlights the importance of considering classification consistency alongside accuracy when studying screening measures and provides the tools and guidance necessary for applied researchers to obtain classification consistency indices in their machine learning research on diagnostic assessments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Machine Learning , Humans , Models, Statistical , Mass Screening
2.
PLoS One ; 19(6): e0301343, 2024.
Article in English | MEDLINE | ID: mdl-38833478

ABSTRACT

The dinoflagellate Alexandrium catenella is a well-known paralytic shellfish toxin producer that forms harmful algal blooms, repeatedly causing damage to Chilean coastal waters. The causes and behavior of algal blooms are complex and vary across different regions. As bacterial interactions with algal species are increasingly recognized as a key factor driving algal blooms, the present study identifies several bacterial candidates potentially associated with Chilean Alexandrium catenella. This research narrowed down the selection of bacteria from the Chilean A. catenella culture using antibiotic treatment and 16S rRNA metabarcoding analysis. Subsequently, seawater from two Chilean coastal stations, Isla Julia and Isla San Pedro, was monitored for two years to detect Alexandrium species and the selected bacteria, utilizing 16S and 18S rRNA gene metabarcoding analyses. The results suggested a potential association between Alexandrium species and Spongiibacteraceae at both stations. The proposed candidate bacteria within the Spongiibacteraceae family, potentially engaging in mutualistic relationships with Alexandrium species, included the genus of BD1-7 clade, Spongiibbacter, and Zhongshania.


Subject(s)
Dinoflagellida , RNA, Ribosomal, 16S , Symbiosis , Dinoflagellida/genetics , Dinoflagellida/physiology , Chile , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Bacteria/classification , Harmful Algal Bloom , Seawater/microbiology , Phylogeny , RNA, Ribosomal, 18S/genetics
3.
Sci Total Environ ; 928: 172374, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38615760

ABSTRACT

The Reloncaví estuary in southern Chile is famous for its aquaculture. However, recurring harmful algal blooms have adversely affected mussel production. Therefore, regular monitoring of algal toxins is urgently needed to better understand the contamination status of the estuary. In this study, we quantified 15 types of lipophilic shellfish toxins in Metri Bay in the Reloncaví estuary on a biweekly basis for 4 years. We identified algal species using microscopy and metabarcoding analysis. We also measured water temperature, salinity, chlorophyll-a, and dissolved oxygen to determine the potential relationships of these parameters with algal toxin production. Our results revealed the presence of a trace amount of pectenotoxin and the causal phytoplankton Dinophysis, as well as yessotoxin and the causal phytoplankton Protoceratium. Statistical analysis indicated that fluctuations in water temperature affected the detection of these toxins. Additionally, metabarcoding analysis detected the highly toxic phytoplankton Alexandrium spp. in some samples. Although our results suggest that the level of lipophilic shellfish toxins in Metri Bay during the study period was insignificantly low using our current LC-MS method, the confirmed presence of highly toxic algae in Metri Bay raises concerns, given that favorable environmental conditions could cause blooms.


Subject(s)
Environmental Monitoring , Estuaries , Harmful Algal Bloom , Marine Toxins , Phytoplankton , Chile , Marine Toxins/analysis , Animals , Dinoflagellida
4.
bioRxiv ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38617301

ABSTRACT

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

5.
Molecules ; 29(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38611939

ABSTRACT

Biosynthesized silver nanoparticles (AgNPs) are widely used in varied applications, which are morphology dependent. Consequently, a morphology-controlled synthesis is mandatory. Although there are several studies focused on the plant extract-based biosynthesis of metallic nanoparticles, the use of extracts obtained from agro-wastes is scant. Furthermore, information regarding morphology modification through the use of additional agents is even more scarce. Thus, in this study, AgNPs were synthesized using a malt extract (ME) obtained from an artisanal beer brewing process residue. Additionally, sodium chloride (NaCl), gum arabic (GA), and talc (T) were used in an attempt to modify the morphology of AgNPs. XRD, DLS, SEM, and TEM results demonstrate that stable AgNPs of different sizes and shapes were synthesized. FTIR, HPLC analysis, and the quantification of total proteins, free amino acids, reducing sugars, and total polyphenols before and after AgNPs synthesis showed that ME biomolecules allowed them to act as a source of reducing and stabilizing agents. Therefore, this study provides evidence that ME can be successfully used to biosynthesize AgNPs. Additionally, the antibacterial activity of AgNPs against Gram-negative and Gram-positive bacteria was evaluated. Results indicate that AgNPs show a higher antibacterial activity against Gram-positive bacteria.


Subject(s)
Acacia , Metal Nanoparticles , Beer , Silver , Anti-Bacterial Agents/pharmacology , Sodium Chloride
6.
Harmful Algae ; 133: 102608, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38485442

ABSTRACT

The study of marine toxins in shellfish is of the utmost importance to ensure people's food safety. Marine toxins in shellfish and microalgae in the water column off the south-central coast of Chile (36°â€’43° S) were studied in a network of 64 stations over a 14-month period. The relative abundance of harmful species Alexandrium catenella, Alexandrium ostenfeldii, Protoceratium reticulatum, Dinophysis acuminata, Dinophysis acuta, Pseudo-nitzschia seriata group and P. delicatissima group was analyzed. The detection and quantification of lipophilic toxins and domoic acid (DA) in shellfish was determined by UHPLC-MS/MS, and for Paralytic Shellfish Toxins (PSTs) by HPLC-FD with post-column oxidation, while for a culture of A. ostenfeldii a Hylic-UHPLC-MS/MS was used. Results showed that DA, gonyautoxin (GTX)-2, GTX-3 and pectenotoxin (PTX)-2 were detected below the permitted limits, while Gymnodimine (GYM)-A and 13-desmethylespirolide C (SPX-1) were below the limit of quantitation. According to the distribution and abundance record of microalgae, DA would be associated to P. seriata and P. delicatissima-groups, PTX-2 to D. acuminata, and GTX-2, GTX-3, GYM-A, and SPX-1 to A. ostenfeldii. However, the toxin analysis of an A. ostenfeldii culture from the Biobío region only showed the presence of the paralytic toxins C2, GTX-2, GTX-3, GTX-5 and saxitoxin, therefore, the source of production of GYM and SPX is still undetermined.


Subject(s)
Dinoflagellida , Heterocyclic Compounds, 3-Ring , Hydrocarbons, Cyclic , Imines , Microalgae , Humans , Tandem Mass Spectrometry , Chile , Marine Toxins/analysis , Shellfish/analysis , Seafood/analysis
7.
Laryngoscope ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38529708

ABSTRACT

The laryngeal adductor reflex (LAR) is a brainstem reflex that closes the vocal fold and constitutes a new method for continuously monitoring the vagus and laryngeal nerves during different surgeries. Previous reports concluded that topical lidocaine in spray inhibited LAR responses. However, topical anesthesia in the upper airway may be necessary in awake intubation. We present six patients who underwent neck endocrine surgery due to an intrathoracic goiter that compromised the airway. Before awake intubation, a nebulization of lidocaine 5% was applied for at least 10 min. The intubation procedure was well tolerated, and bilateral LAR with suitable amplitudes for monitoring was obtained in all cases. In our series, the nebulization of lidocaine 5% did not affect the laryngeal adductor reflex. Laryngoscope, 2024.

8.
Front Surg ; 11: 1366190, 2024.
Article in English | MEDLINE | ID: mdl-38464665

ABSTRACT

Background: Tridimensional medical knowledge of human anatomy is a key step in the undergraduate and postgraduate medical education, especially in surgical fields. Training simulation before real surgical procedures is necessary to develop clinical competences and to minimize surgical complications. Methods: Latex injection of vascular system in brain and in head-neck segment is made after washing out of the vascular system and fixation of the specimen before and after latex injection. Results: Using this latex injection technique, the vascular system of 90% of brains and 80% of head-neck segments are well-perfused. Latex-injected vessels maintain real appearance compared to silicone, and more flexible vessels compared to resins. Besides, latex makes possible a better perfusion of small vessels. Conclusions: Latex vascular injection technique of the brain and head-neck segment is a simulation model for neurosurgical training based on real experiencing to improve surgical skills and surgical results.

9.
Clin Nephrol Case Stud ; 12: 17-21, 2024.
Article in English | MEDLINE | ID: mdl-38352852

ABSTRACT

Waldenström's disease is a rare lymphoproliferative syndrome in the bone marrow and sometimes in lymphoid organs which secretes high amounts of monoclonal immunoglobulin M into serum. It can remain indolent for years and rarely affects the kidney, with intraglomerular rather than intratubular damage being predominant, in contrast to multiple myeloma. Different studies identified AL amyloidosis as the most frequent renal lesion, followed by cryoglobulinemic glomerulonephritis. Signs and symptoms may be unspecific, as well as renal manifestations, so collaboration between nephrologists, hematologists, and pathologists is crucial to establish the role of paraprotein in the development of renal damage. We present an atypical case of Waldenström's disease that had a minimal monoclonal peak and clinically debuted with nephritic and nephrotic syndromes. The diagnosis was cryoglobulinemic glomerulonephritis. Currently, there are numerous treatment options, without enough evidence yet to establish a standardised treatment.

10.
Neuron ; 112(6): 959-971.e8, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38266644

ABSTRACT

For decades, the expression of immediate early genes (IEGs) such as FOS has been the most widely used molecular marker representing neuronal activation. However, to date, there is no equivalent surrogate available for the decrease of neuronal activity. Here, we developed an optogenetic-based biochemical screen in which population neural activities can be controlled by light with single action potential precision, followed by unbiased phosphoproteomic profiling. We identified that the phosphorylation of pyruvate dehydrogenase (pPDH) inversely correlated with the intensity of action potential firing in primary neurons. In in vivo mouse models, monoclonal antibody-based pPDH immunostaining detected activity decreases across the brain, which were induced by a wide range of factors including general anesthesia, chemogenetic inhibition, sensory experiences, and natural behaviors. Thus, as an inverse activity marker (IAM) in vivo, pPDH can be used together with IEGs or other cell-type markers to profile and identify bi-directional neural dynamics induced by experiences or behaviors.


Subject(s)
Brain , Neurons , Mice , Animals , Phosphorylation , Brain/metabolism , Neurons/physiology , Oxidoreductases/genetics , Oxidoreductases/metabolism , Pyruvates/metabolism , Genes, Immediate-Early
11.
New Microbes New Infect ; 57: 101210, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38261949

ABSTRACT

Here we report a case of septic arthritis associated with a genetically divergent Francisella philomiragia strain in a patient with chronic rheumatoid arthritis and Adult-onset Still's disease (AOSD) in Maldonado, Uruguay. In this study mass spectrometry together with whole-genome sequencing using Oxford Nanopore technology allowed for the correct identification of the etiologic agent.

12.
J Consult Clin Psychol ; 92(1): 44-53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37768631

ABSTRACT

OBJECTIVE: Effective psychosocial interventions exist for numerous mental health conditions. However, despite decades of research, limited progress has been made in clarifying the mechanisms that account for their beneficial effects. We know that many treatments work, but we know relatively little about why they work. Mechanisms of change may be obscured due to prior research collapsing across heterogeneous subgroups of patients with differing underlying mechanisms of response. Studies identifying baseline individual characteristics that predict differential response (i.e., moderation) may inform research on why (i.e., mediation) a particular subgroup has better outcomes to an intervention via tests of moderated mediation. METHOD: In a recent randomized controlled trial comparing a 4-week meditation app with a control condition in school system employees (N = 662), we previously developed a "Personalized Advantage Index" (PAI) using baseline characteristics, which identified a subgroup of individuals who derived relatively greater benefit from meditation training. Here, we tested whether the effect of mindfulness acquisition in mediating group differences in outcome was moderated by PAI scores. RESULTS: A significant index of moderated mediation (IMM = 1.22, 95% CI [0.30, 2.33]) revealed that the effect of mindfulness acquisition in mediating group differences in outcome was only significant among those individuals with PAI scores predicting relatively greater benefit from the meditation app. CONCLUSIONS: Subgroups of individuals may differ meaningfully in the mechanisms that mediate their response to an intervention. Considering subgroup-specific mediators may accelerate progress on clarifying mechanisms of change underlying psychosocial interventions and may help inform which specific interventions are most beneficial for whom. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Meditation , Mental Disorders , Mindfulness , Humans , Schools
13.
Curr Biol ; 33(24): 5439-5455.e7, 2023 12 18.
Article in English | MEDLINE | ID: mdl-38056461

ABSTRACT

Neuropeptide S (NPS) is a highly conserved peptide found in all tetrapods that functions in the brain to promote heightened arousal; however, the subpopulations mediating these phenomena remain unknown. We generated mice expressing Cre recombinase from the Nps gene locus (NpsCre) and examined populations of NPS+ neurons in the lateral parabrachial area (LPBA), the peri-locus coeruleus (peri-LC) region of the pons, and the dorsomedial thalamus (DMT). We performed brain-wide mapping of input and output regions of NPS+ clusters and characterized expression patterns of the NPS receptor 1 (NPSR1). While the activity of all three NPS+ subpopulations tracked with vigilance state, only NPS+ neurons of the LPBA exhibited both increased activity prior to wakefulness and decreased activity during REM sleep, similar to the behavioral phenotype observed upon NPSR1 activation. Accordingly, we found that activation of the LPBA but not the peri-LC NPS+ neurons increased wake and reduced REM sleep. Furthermore, given the extended role of the LPBA in respiration and the link between behavioral arousal and breathing rate, we demonstrated that the LPBA but not the peri-LC NPS+ neuronal activation increased respiratory rate. Together, our data suggest that NPS+ neurons of the LPBA represent an unexplored subpopulation regulating breathing, and they are sufficient to recapitulate the sleep/wake phenotypes observed with broad NPS system activation.


Subject(s)
Neuropeptides , Mice , Animals , Neuropeptides/genetics , Neuropeptides/metabolism , Arousal/physiology , Brain/physiology , Wakefulness/physiology , Sleep/physiology , Neurons/physiology , Respiration
14.
Electronics (Basel) ; 12(17)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37974898

ABSTRACT

Inertial kinetics and kinematics have substantial influences on human biomechanical function. A new algorithm for Inertial Measurement Unit (IMU)-based motion tracking is presented in this work. The primary aims of this paper are to combine recent developments in improved biosensor technology with mainstream motion-tracking hardware to measure the overall performance of human movement based on joint axis-angle representations of limb rotation. This work describes an alternative approach to representing three-dimensional rotations using a normalized vector around which an identified joint angle defines the overall rotation, rather than a traditional Euler angle approach. Furthermore, IMUs allow for the direct measurement of joint angular velocities, offering the opportunity to increase the accuracy of instantaneous axis of rotation estimations. Although the axis-angle representation requires vector quotient algebra (quaternions) to define rotation, this approach may be preferred for many graphics, vision, and virtual reality software applications. The analytical method was validated with laboratory data gathered from an infant dummy leg's flexion and extension knee movements and applied to a living subject's upper limb movement. The results showed that the novel approach could reasonably handle a simple case and provide a detailed analysis of axis-angle migration. The described algorithm could play a notable role in the biomechanical analysis of human joints and offers a harbinger of IMU-based biosensors that may detect pathological patterns of joint disease and injury.

15.
ACS Nano ; 17(20): 19865-19876, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37801330

ABSTRACT

Transition metal intercalated transition metal dichalcogenides (TMDs) are promising platforms for next-generation spintronic devices based on their wide range of electronic and magnetic phases, which can be tuned by varying the host lattice or intercalant's identity, stoichiometry, or spatial order. Some of these compounds host a chiral magnetic phase in which the helical winding of magnetic moments propagates along a high-symmetry crystalline axis. Previous studies have demonstrated that variation in intercalant concentrations can have a dramatic effect on the formation of chiral domains and ensemble magnetic properties. However, a systematic and comprehensive study of how atomic-scale order and disorder impact these chiral magnetic textures is so far lacking. Here, we leverage a combination of imaging modes in the (scanning) transmission electron microscope (S/TEM) to directly probe (dis)order across multiple length scales and show how subtle changes in the atomic lattice can tune the mesoscale spin textures and bulk magnetic response in Cr1/3NbS2, with direct implications for the fundamental understanding and technological implementation of such compounds.

16.
Jpn Dent Sci Rev ; 59: 289-302, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37680614

ABSTRACT

In the era of 'precision medicine', liquid biopsies based on cell-free DNA (cfDNA) have emerged as a promising tool in the oncology field. cfDNA from cancer patients is a mixture of tumoral (ctDNA) and non-tumoral DNA originated from healthy, cancer and tumor microenvironmental cells. Apoptosis, necrosis, and active secretion from extracellular vesicles represent the main mechanisms of cfDNA release into the physiological body fluids. Focused on HNC, two main types of cfDNA can be identified: the circulating cfDNA (ccfDNA) and the salivary cfDNA (scfDNA). Numerous studies have reported on the potential of cfDNA analysis as potential diagnostic, prognostic, and monitoring biomarker for HNC. Thus, ctDNA has emerged as an attractive strategy to detect cancer specific genetic and epigenetic alterations including DNA somatic mutations and DNA methylation patterns. This review aims to provide an overview of the up-to-date studies evaluating the value of the analysis of total cfDNA, cfDNA fragment length, and ctDNA analysis at DNA mutation and methylation level in HNC patients.

17.
Chem Mater ; 35(17): 7239-7251, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37719035

ABSTRACT

Magnetic materials with noncollinear spin textures are promising for spintronic applications. To realize practical devices, control over the length and energy scales of such spin textures is imperative. The chiral helimagnets Cr1/3NbS2 and Cr1/3TaS2 exhibit analogous magnetic-phase diagrams with different real-space periodicities and field dependence, positioning them as model systems for studying the relative strengths of the microscopic mechanisms giving rise to exotic spin textures. Although the electronic structure of the Nb analogue has been experimentally investigated, the Ta analogue has received far less attention. Here, we present a comprehensive suite of electronic structure studies on both Cr1/3NbS2 and Cr1/3TaS2 using angle-resolved photoemission spectroscopy and density functional theory. We show that bands in Cr1/3TaS2 are more dispersive than their counterparts in Cr1/3NbS2, resulting in markedly different Fermi wavevectors. The fact that their qualitative magnetic phase diagrams are nevertheless identical shows that hybridization between the intercalant and host lattice mediates the magnetic exchange interactions in both of these materials. We ultimately find that ferromagnetic coupling is stronger in Cr1/3TaS2, but larger spin-orbit coupling (and a stronger Dzyaloshinskii-Moriya interaction) from the heavier host lattice ultimately gives rise to shorter spin textures.

18.
Psychol Methods ; 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37307356

ABSTRACT

Moderation analysis is used to study under what conditions or for which subgroups of individuals a treatment effect is stronger or weaker. When a moderator variable is categorical, such as assigned sex, treatment effects can be estimated for each group resulting in a treatment effect for males and a treatment effect for females. If a moderator variable is a continuous variable, a strategy for investigating moderated treatment effects is to estimate conditional effects (i.e., simple slopes) via the pick-a-point approach. When conditional effects are estimated using the pick-a-point approach, the conditional effects are often given the interpretation of "the treatment effect for the subgroup of individuals…." However, the interpretation of these conditional effects as subgroup effects is potentially misleading because conditional effects are interpreted at a specific value of the moderator variable (e.g., +1 SD above the mean). We describe a simple solution that resolves this problem using a simulation-based approach. We describe how to apply this simulation-based approach to estimate subgroup effects by defining subgroups using a range of scores on the continuous moderator variable. We apply this method to three empirical examples to demonstrate how to estimate subgroup effects for moderated treatment and moderated mediated effects when the moderator variable is a continuous variable. Finally, we provide researchers with both SAS and R code to implement this method for similar situations described in this paper. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

19.
Curr Res Microb Sci ; 4: 100194, 2023.
Article in English | MEDLINE | ID: mdl-37346179

ABSTRACT

Harmful Algal Blooms (HABs) have caused damage to the marine environment in Isla San Pedro in the Gulf of Corcovado, Chile. While rising water temperature and artificial eutrophication are the most discussed topics as a cause, marine bacteria is a recent attractive parameter as an algal bloom driver. This study monitored algal and bacterial compositions in the water of Isla San Pedro for one year using microscopy and 16S rRNA metabarcoding analysis, along with physicochemical parameters. The collected data were analyzed with various statistical tools to understand how the particle-associated bacteria (PA) and the free-living (FL) bacteria were possibly involved in algal blooms. Both FL and PA fractions maintained a stable bacterial composition: the FL fraction was dominated by Proteobacteria (α-Proteobacteria and γ-Proteobacteria), and Cyanobacteria dominated the PA fraction. The two fractions contained equivalent bacterial taxonomic richness (c.a. 8,000 Operational Taxonomic Units) and shared more than 50% of OTU; however, roughly 20% was exclusive to each fraction. The four most abundant algal genera in the Isla San Pedro water were Thalassiosira, Skeletonema, Chaetoceros, and Pseudo-nitzchia. Statistical analysis identified that the bacterial species Polycyclovorans algicola was correlated with Pseudo-nitzschia spp., and our monitoring data recorded a sudden increase of particle-associated Polycyclovorans algicola shortly after the increase of Pseudo-nitzschia, suggesting that P. algicola may have regression effect on Pseudo-nitzschia spp. The study also investigated the physicochemical parameter effect on algal-bacterial interactions. Oxygen concentration and chlorophyll-a showed a strong correlation with both FL and PA bacteria despite their assemblage differences, suggesting that the two groups had different mechanisms for interacting with algal species.

20.
J Autoimmun ; 139: 103072, 2023 09.
Article in English | MEDLINE | ID: mdl-37336012

ABSTRACT

The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves' disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas.


Subject(s)
Autoimmunity , Graves Disease , Humans , B7-H1 Antigen/genetics , Transcriptome , Graves Disease/genetics , Cell Adhesion Molecules/genetics
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