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1.
Nutrients ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474866

RESUMO

The neural mechanisms underlying susceptibility to eating more in response to large portions (i.e., the portion size effect) remain unclear. Thus, the present study examined how neural responses to portion size relate to changes in weight and energy consumed as portions increase. Associations were examined across brain regions traditionally implicated in appetite control (i.e., an appetitive network) as well as the cerebellum, which has recently been implicated in appetite-related processes. Children without obesity (i.e., BMI-for-age-and-sex percentile < 90; N = 63; 55% female) viewed images of larger and smaller portions of food during fMRI and, in separate sessions, ate four meals that varied in portion size. Individual-level linear and quadratic associations between intake (kcal, grams) and portion size (i.e., portion size slopes) were estimated. The response to portion size in cerebellar lobules IV-VI was associated with the quadratic portion size slope estimated from gram intake; a greater response to images depicting smaller compared to larger portions was associated with steeper increases in intake with increasing portion sizes. Within the appetitive network, neural responses were not associated with portion size slopes. A decreased cerebellar response to larger amounts of food may increase children's susceptibility to overeating when excessively large portions are served.


Assuntos
Sinais (Psicologia) , Tamanho da Porção , Criança , Humanos , Feminino , Masculino , Ingestão de Energia , Comportamento Alimentar/fisiologia , Refeições , Cerebelo
2.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38445993

RESUMO

The optical floating zone crystal growth technique is a well-established method for obtaining large, high-purity single crystals. While the floating zone method has been constantly evolving for over six decades, the development of high-pressure (up to 1000 bar) growth systems has only recently been realized via the combination of laser-based heating sources with an all-metal chamber. While our inaugural high-pressure laser floating zone furnace design demonstrated the successful growth of new volatile and metastable phases, the furnace design faces several limitations with imaging quality, heating profile control, and chamber cooling power. Here, we present a second-generation design of the high-pressure laser floating zone furnace, "Laser Optical Kristallmacher II" (LOKII), and demonstrate that this redesign facilitates new advances in crystal growth by highlighting several exemplar materials: α-Fe2O3, ß-Ga2O3, and La2CuO4+δ. Notably, for La2CuO4+δ, we demonstrate the feasibility and long-term stability of traveling solvent floating zone growth under a record pressure of 700 bar.

3.
JAMA Psychiatry ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324323

RESUMO

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

4.
Cortex ; 173: 34-48, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359511

RESUMO

Morphosyntactic assessments are important for characterizing individuals with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard tests are subject to examiner bias and often fail to differentiate between nfvPPA and logopenic variant PPA (lvPPA). Moreover, relevant neural signatures remain underexplored. Here, we leverage natural language processing tools to automatically capture morphosyntactic disturbances and their neuroanatomical correlates in 35 individuals with nfvPPA relative to 10 healthy controls (HC) and 26 individuals with lvPPA. Participants described a picture, and ensuing transcripts were analyzed via part-of-speech tagging to extract sentence-related features (e.g., subordinating and coordinating conjunctions), verbal-related features (e.g., tense markers), and nominal-related features (e.g., subjective and possessive pronouns). Gradient boosting machines were used to classify between groups using all features. We identified the most discriminant morphosyntactic marker via a feature importance algorithm and examined its neural correlates via voxel-based morphometry. Individuals with nfvPPA produced fewer morphosyntactic elements than the other two groups. Such features robustly discriminated them from both individuals with lvPPA and HCs with an AUC of .95 and .82, respectively. The most discriminatory feature corresponded to subordinating conjunctions was correlated with cortical atrophy within the left posterior inferior frontal gyrus across groups (pFWE < .05). Automated morphosyntactic analysis can efficiently differentiate nfvPPA from lvPPA. Also, the most sensitive morphosyntactic markers correlate with a core atrophy region of nfvPPA. Our approach, thus, can contribute to a key challenge in PPA diagnosis.

5.
Brain Commun ; 6(1): fcae024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370445

RESUMO

Individuals with post-stroke aphasia tend to recover their language to some extent; however, it remains challenging to reliably predict the nature and extent of recovery that will occur in the long term. The aim of this study was to quantitatively predict language outcomes in the first year of recovery from aphasia across multiple domains of language and at multiple timepoints post-stroke. We recruited 217 patients with aphasia following acute left hemisphere ischaemic or haemorrhagic stroke and evaluated their speech and language function using the Quick Aphasia Battery acutely and then acquired longitudinal follow-up data at up to three timepoints post-stroke: 1 month (n = 102), 3 months (n = 98) and 1 year (n = 74). We used support vector regression to predict language outcomes at each timepoint using acute clinical imaging data, demographic variables and initial aphasia severity as input. We found that ∼60% of the variance in long-term (1 year) aphasia severity could be predicted using these models, with detailed information about lesion location importantly contributing to these predictions. Predictions at the 1- and 3-month timepoints were somewhat less accurate based on lesion location alone, but reached comparable accuracy to predictions at the 1-year timepoint when initial aphasia severity was included in the models. Specific subdomains of language besides overall severity were predicted with varying but often similar degrees of accuracy. Our findings demonstrate the feasibility of using support vector regression models with leave-one-out cross-validation to make personalized predictions about long-term recovery from aphasia and provide a valuable neuroanatomical baseline upon which to build future models incorporating information beyond neuroanatomical and demographic predictors.

6.
J Med Entomol ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408183

RESUMO

The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is a frequently encountered and commonly reported human-biting tick species that has been recorded from most of California and parts of southwestern Oregon, southcentral Washington, and northwestern Mexico. Although previous investigators have surveyed populations of D. occidentalis for the presence of Rickettsia species across several regions of California, populations of this tick have not been surveyed heretofore for rickettsiae from Baja California, Oregon, or Washington. We evaluated 1,367 host-seeking, D. occidentalis adults collected from 2015 to 2022 by flagging vegetation at multiple sites in Baja California, Mexico, and Oregon and Washington, United States, using genus- and species-specific assays for spotted fever group rickettsiae. DNA of Rickettsia 364D, R. bellii, and R. tillamookensis was not detected in specimens from these regions. DNA of R. rhipicephali was detected in D. occidentalis specimens obtained from Ensenada Municipality in Baja California and southwestern Oregon, but not from Washington. All ompA sequences of R. rhipichephali that were amplified from individual ticks in southwestern Oregon were represented by a single genotype. DNA of the Ixodes pacificus rickettsial endosymbiont was amplified from specimens collected in southwestern Oregon and Klickitat County, Washington; to the best of our knowledge, this Rickettsia species has never been identified in D. occidentalis. Collectively, these data are consistent with a relatively recent introduction of Pacific Coast ticks in the northernmost extension of its recognized range.

7.
Cortex ; 173: 96-119, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38387377

RESUMO

Word deafness is a rare neurological disorder often observed following bilateral damage to superior temporal cortex and canonically defined as an auditory modality-specific deficit in word comprehension. The extent to which word deafness is dissociable from aphasia remains unclear given its heterogeneous presentation, and some have consequently posited that word deafness instead represents a stage in recovery from aphasia, where auditory and linguistic processing are affected to varying degrees and improve at differing rates. Here, we report a case of an individual (Mr. C) with bilateral temporal lobe lesions whose presentation evolved from a severe aphasia to an atypical form of word deafness, where auditory linguistic processing was impaired at the sentence level and beyond. We first reconstructed in detail Mr. C's stroke recovery through medical record review and supplemental interviewing. Then, using behavioral testing and multimodal neuroimaging, we documented a predominant auditory linguistic deficit in sentence and narrative comprehension-with markedly reduced behavioral performance and absent brain activation in the language network in the spoken modality exclusively. In contrast, Mr. C displayed near-unimpaired behavioral performance and robust brain activations in the language network for the linguistic processing of words, irrespective of modality. We argue that these findings not only support the view of word deafness as a stage in aphasia recovery but also further instantiate the important role of left superior temporal cortex in auditory linguistic processing.

8.
Appetite ; 196: 107289, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38423300

RESUMO

Larger portions of food elicit greater intake than smaller portions of food, particularly when foods are high in energy density (kcal/g; ED). The neural mechanisms underlying this effect remain unclear. The present study used fMRI to assess brain activation to food (higher-ED, lower-ED) and non-food (office supplies) images presented in larger and smaller (i.e., age-appropriate) amounts in 61, 7-8-year-olds (29 male, 32 female) without obesity. Larger amounts of food increased activation in bilateral visual and right parahippocampal areas compared to smaller amounts; greater activation to food amount (larger > smaller) in this cluster was associated with smaller increases in food intake as portions increased. Activation to amount (larger > smaller) was stronger for food than office supplies in primary and secondary visual areas, but, for office supplies only, extended into bilateral parahippocampus, inferior parietal cortex, and additional visual areas (e.g., V7). Activation was greater for higher-vs. lower-ED food images in ventromedial prefrontal cortex for both larger and smaller amounts of food; however, this activation extended into left lateral orbital frontal cortex for smaller amounts only. Activation to food cues did not differ by familial risk for obesity. These results highlight potentially distinct neural pathways for encoding food energy content and quantity.


Assuntos
Encéfalo , Sinais (Psicologia) , Humanos , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Alimentos , Obesidade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Imageamento por Ressonância Magnética
9.
Bone ; 179: 116976, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38042445

RESUMO

Mef2c is a transcription factor that mediates key cellular behaviors that promote endochondral ossification and bone formation. Previously, Mef2c has been shown to regulate Sost transcription via its osteocyte-specific enhancer, ECR5, and conditional deletions of Mef2cfl/fl with either Col1-Cre or Dmp1-Cre produced generalized high bone mass (HBM) consistent with Van Buchem Disease phenotypes. However, Sost-/-; Mef2cfl/fl; Dmp1-Cre mice produced a significantly higher bone mass phenotype that Sost-/- alone suggesting that Mef2c modulates bone mass through additional mechanisms, independent of Sost. To identify new Mef2c transcriptional targets important in bone metabolism, we profiled gene expression by single-cell RNA sequencing in subpopulations of cells isolated from Mef2cfl/fl; Dmp1-Cre and Mef2cfl/fl; Bglap-Cre femurs, both strains exhibiting similar high bone mass phenotypes. However, we found Mef2cfl/fl; Bglap-Cre to also display a growth plate defect characterized by an expansion of several osteoprogenitor subpopulations. Differential gene expression analysis identified a total of 96 up- and 2434 down- regulated genes in Mef2cfl/fl; Bglap-Cre and 176 up- and 1041 down- regulated genes in Mef2cfl/fl; Dmp1-Cre bone cell subpopulations compared to wildtype mice. Mef2c deletion affected the transcriptomes across several cell types including mesenchymal progenitors (MP), osteoprogenitors (OSP), osteoblast (OB), and osteocyte (OCY) subpopulations. Several energy metabolism genes such as Uqcrb, Ndufv2, Ndufs3, Ndufa13, Ndufb9, Ndufb5, Cox6a1, Cox5a, Atp5o, Atp5g2, Atp5b, Atp5 were significantly down regulated in Mef2c-deficient OBs and OCYs, in both strains. Binding motif analysis of promoter regions of differentially expressed genes identified Mef2c binding in Bone Sialoprotein (BSP/Ibsp), a gene known to cause increased trabecular BV/TV in the femurs of Ibsp-/- mice. Immunohistochemical analysis confirmed the absence of Ibsp protein in OBs and OCYs. These findings suggests that the HBM in Sost-/-; Mef2cfl/fl; Dmp1-Cre is caused by a multitude of transcriptional changes in genes that regulate bone formation, two of which are Sost and Ibsp.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Osso e Ossos , Fatores de Transcrição MEF2 , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Osso e Ossos/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica , Fatores de Transcrição MEF2/genética , Osteoblastos/metabolismo , Osteogênese/genética
10.
Adv Sci (Weinh) ; 11(2): e2304698, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37946681

RESUMO

The notion that phonons can carry pseudo-angular momentum has many major consequences, including topologically protected phonon chirality, Berry curvature of phonon band structure, and the phonon Hall effect. When a phonon is resonantly coupled to an orbital state split by its crystal field environment, a so-called vibronic bound state forms. Here, a vibronic bound state is observed in NaYbSe2 , a quantum spin liquid candidate. In addition, field and polarization dependent Raman microscopy is used to probe an angular momentum transfer of ΔJz = ±â„ between phonons and the crystalline electric field mediated by the vibronic bound stat. This angular momentum transfer between electronic and lattice subsystems provides new pathways for selective optical addressability of phononic angular momentum via electronic ancillary states.

11.
Emerg Infect Dis ; 30(1): 151-154, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38147068

RESUMO

Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States.


Assuntos
Emigrantes e Imigrantes , Malária Falciparum , Traço Falciforme , Feminino , Gravidez , Humanos , Oregon , Traço Falciforme/complicações , Emigração e Imigração , Malária Falciparum/diagnóstico
12.
Viruses ; 15(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38140610

RESUMO

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.


Assuntos
Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Masculino , Feminino , Humanos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Progressão da Doença , Mamíferos
13.
Neurobiol Lang (Camb) ; 4(4): 536-549, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37946731

RESUMO

After a stroke, individuals with aphasia often recover to a certain extent over time. This recovery process may be dependent on the health of surviving brain regions. Leukoaraiosis (white matter hyperintensities on MRI reflecting cerebral small vessel disease) is one indication of compromised brain health and is associated with cognitive and motor impairment. Previous studies have suggested that leukoaraiosis may be a clinically relevant predictor of aphasia outcomes and recovery, although findings have been inconsistent. We investigated the relationship between leukoaraiosis and aphasia in the first year after stroke. We recruited 267 patients with acute left hemispheric stroke and coincident fluid attenuated inversion recovery MRI. Patients were evaluated for aphasia within 5 days of stroke, and 174 patients presented with aphasia acutely. Of these, 84 patients were evaluated at ∼3 months post-stroke or later to assess longer-term speech and language outcomes. Multivariable regression models were fit to the data to identify any relationships between leukoaraiosis and initial aphasia severity, extent of recovery, or longer-term aphasia severity. We found that leukoaraiosis was present to varying degrees in 90% of patients. However, leukoaraiosis did not predict initial aphasia severity, aphasia recovery, or longer-term aphasia severity. The lack of any relationship between leukoaraiosis severity and aphasia recovery may reflect the anatomical distribution of cerebral small vessel disease, which is largely medial to the white matter pathways that are critical for speech and language function.

14.
Front Oncol ; 13: 1286861, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954069

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the top five deadliest forms of cancer with very few treatment options. The 5-year survival rate for PDAC is 10% following diagnosis. Cadherin 11 (Cdh11), a cell-to-cell adhesion molecule, has been suggested to promote tumor growth and immunosuppression in PDAC, and Cdh11 inhibition significantly extended survival in mice with PDAC. However, the mechanisms by which Cdh11 deficiency influences PDAC progression and anti-tumor immune responses have yet to be fully elucidated. To investigate Cdh11-deficiency induced changes in PDAC tumor microenvironment (TME), we crossed p48-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) mice with Cdh11+/- mice and performed single-cell RNA sequencing (scRNA-seq) of the non-immune (CD45-) and immune (CD45+) compartment of KPC tumor-bearing Cdh11 proficient (KPC-Cdh11+/+) and Cdh11 deficient (KPC-Cdh11+/-) mice. Our analysis showed that Cdh11 is expressed primarily in cancer-associated fibroblasts (CAFs) and at low levels in epithelial cells undergoing epithelial-to-mesenchymal transition (EMT). Cdh11 deficiency altered the molecular profile of CAFs, leading to a decrease in the expression of myofibroblast markers such as Acta2 and Tagln and cytokines such as Il6, Il33 and Midkine (Mdk). We also observed a significant decrease in the presence of monocytes/macrophages and neutrophils in KPC-Cdh11+/- tumors while the proportion of T cells was increased. Additionally, myeloid lineage cells from Cdh11-deficient tumors had reduced expression of immunosuppressive cytokines that have previously been shown to play a role in immune suppression. In summary, our data suggests that Cdh11 deficiency significantly alters the fibroblast and immune microenvironments and contributes to the reduction of immunosuppressive cytokines, leading to an increase in anti-tumor immunity and enhanced survival.

15.
Obesity (Silver Spring) ; 31(12): 2998-3007, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37794530

RESUMO

OBJECTIVE: The objective of this study was to determine whether children with healthy weight who vary by familial risk for obesity differ in executive functioning. METHODS: Children (age 7-8 years) without obesity (n = 93, 52% male) who differed by familial risk for obesity (based on maternal weight status) completed go/no-go and stop-signal tasks to assess inhibitory control and an N-back task to assess working memory. Dual energy x-ray absorptiometry measured adiposity. Linear and mixed-effect models assessed unique effects and relative importance analysis-quantified relative effects of familial risk and percent body fat. RESULTS: Children at high compared with low familial risk showed worse inhibitory control; however, child adiposity was not associated with inhibitory control. Both high familial risk and greater child adiposity were associated with worse N-back performance when cognitive demand was high (2-back), but not low (0- and 1-back). The relative effect of familial risk on executive functioning was 2.7 to 16 times greater than the relative effect of percent body fat. CONCLUSIONS: These findings provide initial evidence that deficits in executive functioning may precede the development of obesity in children at high familial risk for this disease. Additional family risk studies are needed to elucidate the pathways through which maternal obesity influences child executive functioning and risk for obesity.


Assuntos
Obesidade Pediátrica , Gravidez , Humanos , Masculino , Criança , Feminino , Obesidade Pediátrica/complicações , Obesidade Pediátrica/genética , Predisposição Genética para Doença , Função Executiva , Adiposidade , Aumento de Peso
16.
Pediatr Dent ; 45(5): 380-389, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37904262

RESUMO

Purpose: To conduct a pilot study assessing resident performance and self-efficacy during sedation-related simulations. Methods: Residents completed one informed consent and two sedation-related emergency simulations. Performance was measured for each simulation. Self- efficacy (i. e., confidence) was measured via pre- and post-simulation questionnaires. Descriptive and nonparametric statistics were calculated. Results: Twenty-five residents completed the simulations. Second-year residents performed better than first-year residents in both informed consent and emergency simulations; however, only the informed consent simulation was significant (P<0.02). Self-efficacy significantly increased after completing the simulations (18 percent pre-simulation versus 42.7 percent post-simulation, P<0.001). Residents identified communication skills as an area of improvement after the simulations. For the emergency vignettes, residents expressed feeling inadequate knowledge, problem-solving skills, and teamwork during the simulation. Conclusions: Simulations improved resident confidence in obtaining informed consent and managing certain sedation-related emergencies, but residents felt ill-prepared to manage an emergency. Further study is warranted to understand the best-practice frequency of sedation-related emergency simulation to promote skill retention.


Assuntos
Internato e Residência , Humanos , Criança , Projetos Piloto , Inquéritos e Questionários , Competência Clínica
17.
PLoS Biol ; 21(10): e3002328, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37862379

RESUMO

Morphology is a defining feature of neuronal identity. Like neurons, glia display diverse morphologies, both across and within glial classes, but are also known to be morphologically plastic. Here, we explored the relationship between glial morphology and transcriptional signature using the Drosophila central nervous system (CNS), where glia are categorised into 5 main classes (outer and inner surface glia, cortex glia, ensheathing glia, and astrocytes), which show within-class morphological diversity. We analysed and validated single-cell RNA sequencing data of Drosophila glia in 2 well-characterised tissues from distinct developmental stages, containing distinct circuit types: the embryonic ventral nerve cord (VNC) (motor) and the adult optic lobes (sensory). Our analysis identified a new morphologically and transcriptionally distinct surface glial population in the VNC. However, many glial morphological categories could not be distinguished transcriptionally, and indeed, embryonic and adult astrocytes were transcriptionally analogous despite differences in developmental stage and circuit type. While we did detect extensive within-class transcriptomic diversity for optic lobe glia, this could be explained entirely by glial residence in the most superficial neuropil (lamina) and an associated enrichment for immune-related gene expression. In summary, we generated a single-cell transcriptomic atlas of glia in Drosophila, and our extensive in vivo validation revealed that glia exhibit more diversity at the morphological level than was detectable at the transcriptional level. This atlas will serve as a resource for the community to probe glial diversity and function.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Neurópilo/metabolismo , Astrócitos/metabolismo , Proteínas de Drosophila/metabolismo
18.
Neurobiol Lang (Camb) ; 4(4): 516-535, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841966

RESUMO

Imaging studies of language processing in clinical populations can be complicated to interpret for several reasons, one being the difficulty of matching the effortfulness of processing across individuals or tasks. To better understand how effortful linguistic processing is reflected in functional activity, we investigated the neural correlates of task difficulty in linguistic and non-linguistic contexts in the auditory modality and then compared our findings to a recent analogous experiment in the visual modality in a different cohort. Nineteen neurologically normal individuals were scanned with fMRI as they performed a linguistic task (semantic matching) and a non-linguistic task (melodic matching), each with two levels of difficulty. We found that left hemisphere frontal and temporal language regions, as well as the right inferior frontal gyrus, were modulated by linguistic demand and not by non-linguistic demand. This was broadly similar to what was previously observed in the visual modality. In contrast, the multiple demand (MD) network, a set of brain regions thought to support cognitive flexibility in many contexts, was modulated neither by linguistic demand nor by non-linguistic demand in the auditory modality. This finding was in striking contradistinction to what was previously observed in the visual modality, where the MD network was robustly modulated by both linguistic and non-linguistic demand. Our findings suggest that while the language network is modulated by linguistic demand irrespective of modality, modulation of the MD network by linguistic demand is not inherent to linguistic processing, but rather depends on specific task factors.

20.
Proc Natl Acad Sci U S A ; 120(40): e2308588120, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748057

RESUMO

A recently discovered group of kagome metals AV[Formula: see text]Sb[Formula: see text] (A = K, Rb, Cs) exhibit a variety of intertwined unconventional electronic phases, which emerge from a puzzling charge density wave phase. Understanding of this charge-ordered parent phase is crucial for deciphering the entire phase diagram. However, the mechanism of the charge density wave is still controversial, and its primary source of fluctuations-the collective modes-has not been experimentally observed. Here, we use ultrashort laser pulses to melt the charge order in CsV[Formula: see text]Sb[Formula: see text] and record the resulting dynamics using femtosecond angle-resolved photoemission. We resolve the melting time of the charge order and directly observe its amplitude mode, imposing a fundamental limit for the fastest possible lattice rearrangement time. These observations together with ab initio calculations provide clear evidence for a structural rather than electronic mechanism of the charge density wave. Our findings pave the way for a better understanding of the unconventional phases hosted on the kagome lattice.

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