A rapid transition from subduction to Barrovian metamorphism: geochronology of mafic-ultramafic relicts of oceanic crust in the Central Alps, Switzerland.

Relicts of subducted oceanic lithosphere provide key information for the tectonic reconstructions of convergent margins. In the Central Alps, such relicts occur as isolated mafic-ultramafic lenses within the migmatites of the southern Adula nappe and Cima-Lunga unit. Analysis of the major-, minor-, and accessory minerals of these ophiolitic relicts, combined with zircon and rutile U-Pb ages and zircon oxygen isotopes, allows the reconstruction of different stages of their complex evolution. The mafic-ultramafic suite in Valle di Moleno consists of chlorite-harzburgites associated with metarodingites and retrogressed eclogites. Relic omphacite and kyanite in retrogressed eclogites provide evidence for subduction-related metamorphism. Increasing XPrp in the garnet mantle towards the rim documents heating during high-pressure metamorphism up to 800-850 °C. Polyphase inclusions and chemical zoning in garnet suggest fluid-assisted melting during high-pressure metamorphism dated at 31.0 ± 0.9 Ma. In Val Cama, chlorite-harzburgites, metarodingites and calcsilicate-metasediments occur. Detrital zircon ages in the metasediment suggest a Mesozoic deposition. The metarodingite-metaperidotite-metasediment association and the low δ18O signatures of zircon (δ18O 3.0-3.7‰), inherited from seafloor metasomatism of the protoliths, show that the rocks are derived from former altered oceanic crust. Amphibolite facies metamorphism related to the Central Alps Barrovian evolution in Val Cama occurred at 28.8 ± 1.5 Ma. The combined data from Moleno and Cama indicate a rapid transition (~ 2 Ma) from subduction to collisional metamorphism with corresponding exhumation rates of 3-6 cm/year. Fast exhumation tectonics may have been favored by slab break-off or slab extraction. U-Pb dating of rutile from both localities yields ages of ~ 20 Ma, suggesting that these rocks remained at amphibolite-facies conditions for about 10 Ma and underwent a second fast exhumation of 3 cm/year associated with vertical movements along the Insubric line. Supplementary Information: The online version contains supplementary material available at 10.1186/s00015-024-00462-7.

Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin.

Mucosal-associated invariant T (MAIT) cells represent an abundant innate-like T cell subtype in the human liver. MAIT cells are assigned crucial roles in regulating immunity and inflammation, yet their role in liver cancer remains elusive. Here, we present a MAIT cell-centered profiling of hepatocellular carcinoma (HCC) using scRNA-seq, flow cytometry, and co-detection by indexing (CODEX) imaging of paired patient samples. These analyses highlight the heterogeneity and dysfunctionality of MAIT cells in HCC and their defective capacity to infiltrate liver tumors. Machine-learning tools were used to dissect the spatial cellular interaction network within the MAIT cell neighborhood. Co-localization in the adjacent liver and interaction between niche-occupying CSF1R+PD-L1+ tumor-associated macrophages (TAMs) and MAIT cells was identified as a key regulatory element of MAIT cell dysfunction. Perturbation of this cell-cell interaction in ex vivo co-culture studies using patient samples and murine models reinvigorated MAIT cell cytotoxicity. These studies suggest that aPD-1/aPD-L1 therapies target MAIT cells in HCC patients.

Determination of d- and l-Amino Acids in Garlic Foodstuffs by Liquid Chromatography-Tandem Mass Spectrometry.

Black garlic is currently attracting interest as a health food and constituent of commercial supplements; however, no data regarding the d-amino acids within black garlic have been reported. Therefore, the amino acid compositions of methanol extracts from fresh and black garlic were compared herein. We investigated the contents of the d- and l-forms of amino acids in commercial fresh, black, and freeze-dried garlic foodstuffs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a pre-column chiral derivatization reagent, succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl-5-oxoimidazolidin-4-yl) acetate. Several d-amino acids, namely, the d-forms of Asn, Ala, Ser, Thr, Glu, Asp, Pro, Arg, Phe, Orn, Lys, and Tyr, were observed in the methanol extract of black garlic, whereas only d-Ala was detected in that of fresh garlic foodstuffs. These data suggest that several d-amino acids can be produced during fermentation for preparing black garlic.

Scaling the Children Immunization App (CIMA) to Support Child Refugees and Parents in the Time of the COVID-19 Pandemic: A Social Capital Approach to Scale a Smartphone Application in Zaatari Camp, Jordan.

BACKGROUND: Children vaccination is a key intervention for their survival, especially among refugees. Yet, children vaccination registration is done manually in refugees camps and there is no possibility to send reminders to parents to come back on time. We aimed to boost the parental registration of children's vaccination records on a Children Immunization app (CIMA) while also availing the parents with useful parenting skills under COVID-19-related stress. METHODS: We incorporated United Nations Office on Drugs and Crime (UNODC) Parenting Skills under COVID-19 information material, through CIMA in Arabic and English languages. We recruited 1100 children in February-March 2021, through a community health promotion dissemination approach. A team of two nurses from the local population and two volunteers (one trained nurse and one trained social worker), from the camp, was formed. They promoted the CIMA app at two clinics and through households visits in Zaatari refugee camp. Qualitative data on impressions and observations of the interactions with the Zaatari camp community were also collected. RESULTS: A total of 1100 children, up to 15 months of age, eligible for vaccination were enrolled in CIMA, whereby the staff explained the content of the app in terms of vaccination schedule, health promotion materials for vaccination and parenting skills to their caregivers. During the household visits, the volunteers identified a total of 70 children that have incomplete history of vaccination records (n = 42/70 girls, 60%). Also, opportunities and challenges for scaling the app were documented. CONCLUSION: The scaling of CIMA as an innovative means of dissemination of risk and health information in challenging context such as refugee camps was feasible. In the context of vaccination needs for children, in refugee settings, such a need is more eminent, particularly in the context of COVID-19.

The Consortium for the early identification of Alzheimer's disease-Quebec (CIMA-Q).

INTRODUCTION: The Consortium for the early identification of Alzheimer's disease-Quebec (CIMA-Q) created a research infrastructure to recruit, characterize, and track disease progression in individuals at risk of dementia. METHODS: CIMA-Q established standardized clinical, neuropsychological, neuroimaging, blood (plasma, serum, RNA, genomic DNA), cryopreserved peripheral blood mononuclear cells, and cerebrospinal fluid collection protocols. These data and biological materials are available to the research community. RESULTS: In phase 1, 115 persons with subjective cognitive decline, 88 with mild cognitive impairment, 31 with early probable Alzheimer's disease, and 56 older adults with no worries nor impairments received detailed clinical and cognitive evaluations as well as blood and peripheral blood mononuclear cells collections. Among them, 142 underwent magnetic resonance imaging, 29 a 18fluorodeoxyglucose positron emission tomography, and 60 a lumbar puncture. DISCUSSION: CIMA-Q provides procedures and resources to identify early biomarkers and novel therapeutic targets, and holds promise for detecting cognitive decline in Alzheimer's disease.

Imaging phosphodiesterase-10a availability in cocaine use disorder with [11 C]IMA107 and PET.

Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self-administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder ("cocaine users") compared to controls. PDE10a availability was measured with [11 C]IMA107 and positron emission tomography in 15 cocaine users and 15 controls matched for age, gender, and nicotine status. Cocaine users with no comorbid psychiatric, medical, or drug abuse disorders were scanned following two weeks of outpatient-monitored abstinence. [11 C]IMA107 binding potential relative to nondisplaceable uptake (BPND ) in the regions of interest was derived with the simplified reference tissue method. No significant effect of diagnosis on BPND was demonstrated using linear mixed modeling with [11 C]IMA107 BPND as the dependent variable and regions of interest as a repeated measure. There were no significant relationships between BPND and clinical rating scales. To the extent that PDE10a is a valid proxy for MSN spine density, these results do not support its increase in recently abstinent cocaine users.

La gobernabilidad migratoria en Sudamérica: la difusión de abajo hacia arriba (ascendente) del Acuerdo de Residencia del Mercosur / Migration governance in south america: the bottom-up diffusion of the residence agreement of mercosur / A governança migratória na américa do sul: a difusão de baixo para cima (bottom-up) do acordo de residência do mercosul

Abstract This article offers a complementary explanation to the diffusion theory that focuses on the process of governance emergence from a top-down perspective. This complementary explanation analyzes the bottom-up processes of diffusion and tested them by studying the policy formulation process in the Mercosur Residence Agreement (RA) signed in 2002. Based on interviews with key actors, documents, and academic literature, this article concludes that the RA was mainly the result of Brazilian and Argentinian negotiations. Brazil needed to boost regional cooperation after the Mercosur crisis, and considered that a joint migration amnesty could have a positive impact on the trading bloc's image. However, the Argentinian experience in migration issues allowed for a more coherent policy on the matter. Therefore, I maintain that the mode of interaction in the Residence Agreement negotiations was a bottom up diffusion process that allowed the regionalization of domestic policies.

Resumen Este artículo ofrece una explicación complementaria a la teoría de la difusión que se centra en el proceso de emergencia de la gobernanza desde una perspectiva de arriba hacia abajo (top-down). Esta explicación complementaria analiza los procesos de abajo hacia arriba (bottom-up) de difusión y los prueba mediante el estudio de la formulación de políticas en el Acuerdo de Residencia del Mercosur, firmado en el 2002. En base a entrevistas con actores clave, documentos y literatura académica, este artículo concluye que el Acuerdo fue principalmente el resultado de las negociaciones brasileñas y argentinas. Brasil necesitaba impulsar la cooperación regional después de la crisis del Mercosur y consideró que una amnistía migratoria conjunta podría tener un impacto positivo en la imagen del bloque. Sin embargo, la experiencia argentina en temas de migración permitió una política más coherente en la materia. Por lo tanto, se sostiene que el modo de interacción en las negociaciones del Acuerdo fue un proceso de difusión de abajo hacia arriba (bottom-up) que posibilitó la regionalización de las políticas domésticas.

Resumo Este artigo oferece uma explicação complementar à teoria da difusão que explica o processo de surgimento da governança regional a partir de uma perspectiva de cima para baixo (top-down). Essa explicação complementar analisa os processos de difusão de baixo para cima (bottom-up), e os testa por meio do estudo da formulação de políticas no Acordo de Residência do Mercosul, assinado em 2002. Tomando em consideração entrevistas com atores destacados, documentos e literatura acadêmica, este artigo conclui que o Acordo foi principalmente o resultado das negociações brasileiras e argentinas. O Brasil em um primeiro momento considerou uma anistia migratória regional para melhorar a imagem do Mercosul. No entanto, a experiência argentina em questões de migração permitiu uma política mais coerente na matéria. Portanto, este trabalho conclui que o modo de interação na negociação do Acordo foi um processo de difusão de baixo para cima (bottom-up) que produziu a regionalização de políticas domésticas.

Desviación paroxística de la mirada hacia arriba: estudio de caso / Paroxysmal upgaze deviation: case report / Desvio paroxístico do olhar para cima: estudo de caso

La desviación paroxística de la mirada hacia arriba es un síndrome infantil descrito por primera vez en 1988 y desde entonces solo se registran alrededor de cincuenta reportes en el mundo. Su etiología no es clara y, aunque su pronóstico es variable, la mayoría de los informes señalan que durante el crecimiento los episodios tienden a disminuir en frecuencia y duración hasta desaparecer. El caso que se reporta corresponde a un niño de 16 meses de edad, quien desde los 11 meses presenta episodios de supraversión sostenida de la mirada conjugada de duración variable con flexión cervical compensatoria y nistagmo vertical a la fijación ocular sin alteración del estado de conciencia. Los episodios son de predominio matinal y se exacerban por situaciones de estrés como el ayuno o el insomnio; sin embargo, ceden con la conciliación del sueño. Los exámenes neurológico y oftalmológico resultan normales y a su vez las neuroimágenes y electroencefalograma no tienen hallazgos relevantes.

The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck flexion and down-beat saccades in attempted downgaze. These events are predominantly diurnal, and are exacerbated by stressful situations such as fasting or insomnia, however and improve with sleep. They have normal neurologic and ophthalmologic examination, and neuroimaging and EEG findings are not relevant.

O desvio paroxístico do olhar para cima é um síndrome infantil foi descrito por primeira vez no ano 1988 e desde então só se registram cerca de cinquenta reportes no mundo. Sua etiologia não é clara e, mesmo que seu prognóstico é variável, a maioria dos informes assinalam que durante o crescimento, os episódios tendem a diminuir em frequência e duração até desaparecer. O caso que é reportado corresponde a uma criança de 16 meses de idade, que desde os 11 meses, apresenta episódios de supraversão sustentada do olhar conjugado de duração variável com flexão cervical compensatória e nistagmo vertical à fixação ocular sem alteração do estado de consciência. Os episódios são de predomínio matinal e se exacerbam por situações de estresse como o jejum ou a insônia; no entanto, cedem com a conciliação do sono. Os exames neurológico e oftalmológico resultam normais e a sua vez as neuroimagens e electroencefalograma não têm resultados relevantes.