Proof of Concept Study: Comparability of Microbiome Diversity in Self- and Physician-Collected HPV-Positive and HPV-Negative Cervicovaginal Samples

Recent studies have revealed the impact of human papillomavirus (HPV) infections on the cervicovaginal microbiome; however, few have explored the utility of self-collected specimens (SCS) for microbiome detection, obtained using standardised methods for HPV testing. Here, we present a proof-of-concept analysis utilising Oxford Nanopore sequencing of the 16S rRNA gene in paired samples collected either by the patient using an Evalyn Brush or collected by a physician using liquid-based cytology (LBC). We found no significant differences in the alpha-diversity estimates between the SCS and LBC samples. Similarly, when analysing beta-diversity, we observed a close grouping of paired samples, indicating that both collection methods detected the same microbiome features. The identification of genera and Lactobacillus species in each sample allowed for their classification into community state types (CSTs). Notably, paired samples had the same CST, while HPV-positive and -negative samples belonged to distinct CSTs. As previously described in other studies, HPV-positive samples exhibited heightened bacterial diversity, reduced Lactobacillus abundance, and an increase in genera like Sneathia or Dialister. Altogether, this study showed comparable results between the SCS and LBC samples, underscoring the potential of self-sampling for analysing the microbiome composition in cervicovaginal samples initially collected for HPV testing in the context of cervical cancer screening

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders

Jornada "Experiències d'Aprenentatge Servei a la Universitat de Barcelona". Desenvolupament i experiències presentades.

La Jornada, titulada “Experiències d’Aprenentatge Servei a la Universitat de Barcelona”, te la finalitat de facilitar una reflexió conjunta sobre l’aplicació de l’ApS a la tasca docent i compartir les experiències desenvolupades a la nostra universitat. L'infome presenta el desenvolupament de la jornada i el recull dels pòsters presentats pels participants.ICE-IDP, Grup ApS (UB

Luminous efficiency based on FRIPON meteors and limitations of ablation models

Context. In meteor physics, the luminous efficiency τ is used to convert the meteor's magnitude to the corresponding meteoroid's mass. However, a lack of sufficiently accurate verification methods or adequate laboratory tests mean that discussions around this parameter are a subject of controversy. Aims: In this work, we aim to use meteor data obtained by the Fireball Recovery and InterPlanetary Observation to calculate the luminous efficiencies of the recorded meteors. We also show the limitations of the methods presented herein. Methods: Deceleration-based formulas were used to calculate the masses of the pre-atmospheric meteoroids. These can in turn be compared to the meteor brightnesses to assess the luminous efficiencies of the recorded objects. Fragmentation of the meteoroids is not considered within this model. Good measurements of the meteor deceleration are required. Results: We find τ-values, as well as the shape change coefficients, of 294 meteors and fireballs with determined masses in the range of 10^−6 / -100 kg. The derived τ-values have a median of τ_median = 2.17%. Most of them are of the order of 0.1-10%. We present how our values are obtained, compare them with data reported in the literature, and discuss several methods. A dependence of τ on the pre-atmospheric velocity of the meteor, ve, is noticeable with a relation of τ = 0.0023⋅ve^2.3. Furthermore, a dependence of τ on the initial meteoroid mass, Me, is found with negative linear behaviour in log-log space: τ = 0.48⋅Me/−0.47. Conclusions: The higher luminous efficiency of fast meteors could be explained by the higher amount of energy released. Fast meteoroids produce additional emission lines that radiate more efficiently in specific wavelengths due to the appearance of the so-called second component of higher temperature. Furthermore, the negative dependence of τ on Me implies that the radiation of smaller meteoroids is more efficient. The results of this study also show the limitations of the ablation-based model for the determination of the luminous efficiency

Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis

Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ -knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery

Luminous efficiency of meteors derived from ablation model after assessment of its range of validity

Context. The luminous efficiency, τ, can be used to compute the pre-atmospheric masses of meteoroids from corresponding recorded meteor brightnesses. The derivation of the luminous efficiency is non-trivial and is subject to biases and model assumptions. This has led to greatly varying results in the last decades of studies. Aims: The present paper aims to investigate how a reduction in various observational biases can be achieved to derive (more) reliable values for the luminous efficiency. Methods: A total of 281 meteors observed by the Fireball Recovery and InterPlanetary Observation Network (FRIPON) are studied. The luminous efficiencies of the events are computed using an ablation-based model. The relations of τ as a function of the pre-atmospheric meteoroid velocity, ve, and mass, Me, are studied. Various aspects that could render the method less valid, cause inaccuracies, or bias the results are investigated. On this basis, the best suitable meteors were selected for luminous efficiency computations. Results: The presented analysis shows the limits of the used method. The most influential characteristics that are necessary for reliable results for the τ computation were identified. We study the dependence of τ on the assumed meteoroid's density, ρ, and include improved ρ-values for objects with identified meteoroid stream association. Based on the discovered individual biases and constraints we create a pre-debiased subset of 54 well-recorded events with a relative velocity change >80%, a final height <70 km, and a Knudsen number Kn < 0.01; this last value indicates that the events were observed in the continuum-flow regime. We find τ-values in the range between 0.012% and 1.1% for this pre-debiased subset and relations of τ to ve and Me of: τ=7.33⋅ve^−1.10 and τ=0.28⋅Me^−0.33. Conclusions: The derived luminous efficiency of meteoroids depends on the assumed material density. Our results indicate that the applied debiasing method improves the analysis of τ from decelerated meteoroids. The underlying method is only valid for meteors in the continuum-flow regime. These events tend to have low end heights, large masses, and high deceleration

Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis

Abstract Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient’s blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4–5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery