Dendritic cells (DCs) control innate and adaptive immunity by patrolling tissues to gather antigens and danger signals derived from microbes and tissue. Subsequently, DCs integrate those ...environmental cues, orchestrate immunity or tolerance, and regulate tissue homeostasis. Recent advances in the field of immunometabolism highlight the notion that immune cells markedly alter cellular metabolic pathways during differentiation or upon activation, which has important implications on their functionality. Previous studies showed that active oxidative phosphorylation in mitochondria is associated with immature or tolerogenic DCs, while increased glycolysis upon pathogen sensing can promote immunogenic DC functions. However, new results in the last years suggest that regulation of DC metabolism in steady state, after immunogenic activation and during tolerance in different pathophysiological settings, may be more complex. Moreover, ontogenically distinct DC subsets show different functional specializations to control T cell responses. It is, thus, relevant how metabolism influences DC differentiation and plasticity, and what potential metabolic differences exist among DC subsets. Better understanding of the emerging connection between metabolic adaptions and functional DC specification will likely allow the development of therapeutic strategies to manipulate immune responses.
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8
T cells with a resident memory (Trm) phenotype ...correlates with improved survival. However, the interplay of circulating CD8
T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8
T cells subsets needed for optimal tumour vaccination and immunotherapy.
The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen ...affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11cΔVhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo. VHL-deficient phenotype is intrinsic in AMs derived from monocyte precursors in mixed bone marrow chimeras. Moreover, unlike control Vhlfl/fl, AMs from CD11cΔVhl mice do not reverse pulmonary alveolar proteinosis when transplanted into Csf2rb−/− mice, demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our results suggest that optimal AM terminal differentiation, self-renewal, and homeostatic function requires their intact oxygen-sensing capacity.
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•Hypoxia and glycolysis signatures are downregulated during alveolar macrophage maturation•VHL-deficient alveolar macrophages induce HIF-target genes and are more glycolytic•VHL-deficient alveolar macrophages show an intrinsic immature-like phenotype•VHL promotes alveolar macrophage self-renewal and surfactant clearance capacity
Izquierdo et al. show that the absence of VHL in lung alveolar macrophages prevents their terminal maturation. VHL-deficient alveolar macrophages induce HIF-target gene expression and are partially desensitized to oxygen. Moreover, they have a decreased self-renewal and surfactant clearance capacity, suggesting that oxygen sensing contributes to alveolar macrophage functional maturation.
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8(+) T cells with a resident memory (Trm) ...phenotype correlates with improved survival. However, the interplay of circulating CD8(+) T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8(+) T cells subsets needed for optimal tumour vaccination and immunotherapy.
This paper evaluates the accuracy of shoreline positions obtained from the infrared (IR) bands of Landsat 7, Landsat 8, and Sentinel-2 imagery on natural beaches. A workflow for sub-pixel shoreline ...extraction, already tested on seawalls, is used. The present work analyzes the behavior of that workflow and resultant shorelines on a micro-tidal (<20 cm) sandy beach and makes a comparison with other more accurate sets of shorelines. These other sets were obtained using differential GNSS surveys and terrestrial photogrammetry techniques through the C-Pro monitoring system. 21 sub-pixel shorelines and their respective high-precision lines served for the evaluation. The results prove that NIR bands can easily confuse the shoreline with whitewater, whereas SWIR bands are more reliable in this respect. Moreover, it verifies that shorelines obtained from bands 11 and 12 of Sentinel-2 are very similar to those obtained with bands 6 and 7 of Landsat 8 (−0.75 ± 2.5 m; negative sign indicates landward bias). The variability of the brightness in the terrestrial zone influences shoreline detection: brighter zones cause a small landward bias. A relation between the swell and shoreline accuracy is found, mainly identified in images obtained from Landsat 8 and Sentinel-2. On natural beaches, the mean shoreline error varies with the type of image used. After analyzing the whole set of shorelines detected from Landsat 7, we conclude that the mean horizontal error is 4.63 m (±6.55 m) and 5.50 m (±4.86 m), respectively, for high and low gain images. For the Landsat 8 and Sentinel-2 shorelines, the mean error reaches 3.06 m (±5.79 m).
Sequencing variable regions of the 16S rRNA gene (≃300 bp) with Illumina technology is commonly used to study the composition of human microbiota. Unfortunately, short reads are unable to ...differentiate between highly similar species. Considering that species from the same genus can be associated with health or disease it is important to identify them at the lowest possible taxonomic rank. Third-generation sequencing platforms such as PacBio SMRT, increase read lengths allowing to sequence the whole gene with the maximum taxonomic resolution. Despite its potential, full length 16S rRNA gene sequencing is not widely used yet. The aim of the current study was to compare the sequencing output and taxonomic annotation performance of the two approaches (Illumina short read sequencing and PacBio long read sequencing of 16S rRNA gene) in different human microbiome samples. DNA from saliva, oral biofilms (subgingival plaque) and faeces of 9 volunteers was isolated. Regions V3-V4 and V1-V9 were amplified and sequenced by Illumina Miseq and by PacBio Sequel II sequencers, respectively.
With both platforms, a similar percentage of reads was assigned to the genus level (94.79% and 95.06% respectively) but with PacBio a higher proportion of reads were further assigned to the species level (55.23% vs 74.14%). Regarding overall bacterial composition, samples clustered by niche and not by sequencing platform. In addition, all genera with > 0.1% abundance were detected in both platforms for all types of samples. Although some genera such as Streptococcus tended to be observed at higher frequency in PacBio than in Illumina (20.14% vs 14.12% in saliva, 10.63% vs 6.59% in subgingival plaque biofilm samples) none of the differences were statistically significant when correcting for multiple testing.
The results presented in the current manuscript suggest that samples sequenced using Illumina and PacBio are mostly comparable. Considering that PacBio reads were assigned at the species level with higher accuracy than Illumina, our data support the use of PacBio technology for future microbiome studies, although a higher cost is currently required to obtain an equivalent number of reads per sample.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The paper explores some mechanisms of corporate governance (ownership and board characteristics) in Spanish listed companies and their impact on the likelihood of financial distress. An empirical ...study was conducted between 2007 and 2012 using a matched-pairs research design with 308 observations, with half of them classified as distressed and non-distressed. Based on the previous study by Pindado, Rodrigues, and De la Torre (2008), a broader concept of bankruptcy is used to define business failure. Employing several conditional logistic models, as well as to other previous studies on bankruptcy, the results confirm that in difficult situations prior to bankruptcy, the impact of board ownership and proportion of independent directors on business failure likelihood are similar to those exerted in more extreme situations. These results go one step further, to offer a negative relationship between board size and the likelihood of financial distress. This result is interpreted as a form of creating diversity and to improve the access to the information and resources, especially in contexts where the ownership is highly concentrated and large shareholders have a great power to influence the board structure. However, the results confirm that ownership concentration does not have a significant impact on financial distress likelihood in the Spanish context. It is argued that large shareholders are passive as regards an enhanced monitoring of management and, alternatively, they do not have enough incentives to hold back the financial distress. These findings have important implications in the Spanish context, where several changes in the regulatory listing requirements have been carried out with respect to corporate governance, and where there is no empirical evidence regarding this respect.
Este trabajo analiza algunos mecanismos de gobierno corporativo (propiedad y características del Consejo de Administración) en las empresas cotizadas españolas y su impacto sobre las probabilidades de fracaso empresarial. Usando la técnica del emparejamiento, se lleva a cabo un estudio empírico con 308 observaciones, la mitad de ellas fracasadas y la otra mitad no fracasadas entre 2007 y 2012. Sobre la base del estudio de Pindado et al. (2008), se ha usado un concepto amplio de fracaso empresarial. Empleando modelos logísticos condicionales, y adicionalmente a otros estudios previos sobre fracaso empresarial, nuestros resultados confirman que en situaciones de dificultad previas a la quiebra, la propiedad de los consejeros y la proporción de consejeros independientes ejercen un impacto similar sobre la probabilidad de fracaso empresarial a otras situaciones de fracaso más extremas. Nuestros resultados van más allá al evidenciar una relación negativa entre el tamaño del consejo y la probabilidad de fracaso empresarial. Interpretamos estos resultados como una forma de creación de diversidad y mejorar el acceso a la información y a los recursos, especialmente en contextos donde la propiedad está altamente concentrada y los grandes accionistas tienen un gran poder de influencia en la composición de la estructura del consejo. Sin embargo, los resultados confirman que la concentración de la propiedad no tiene un efecto significativo sobre la probabilidad de fracaso empresarial en el contexto español. Interpretamos que los accionistas mayoritarios son pasivos con respecto a una mayor vigilancia de la gestión y alterativamente, no tiene suficientes incentivos para frenar las dificultades financieras. Estos resultados tienen importantes implicaciones en el contexto español donde se han propuesto cambios en los requerimientos relativos al gobierno corporativo y donde no hay evidencia empírica a este respecto.
Previous studies of corporate governance and the likelihood of business failure have focused on the role of large shareholders as owners; especially on the role that institutional shareholders play ...in management control. However, scant attention has been paid to the role of institutional shareholders as board members. To contribute towards an understanding of this issue, our study examines experimentally the role of institutional shareholders in business financial distress likelihood within the contexts of ownership concentration. We study not only the different roles of institutional shareholders as owners and board members, but also consider the diverse set of institutional shareholders' interests, categorised into pressure-resistant and pressure-sensitive. We find that directors appointed by pressure-resistant institutional shareholders, such as investment funds, pension funds, venture capital and holding firms, have a negative impact on the likelihood of business failure. This result indicates that institutional owners insist on directorships when the firm is important to them or when they judge they can keep a firm from going into distress, particularly in the context of concentrated ownership. In particular, the risk of failure acts as a catalyst to trigger reactions from the pressure-resistant institutional shareholders in the form of organizational changes in the firm. In contrast, directors appointed by pressure-sensitive shareholders have no impact on the likelihood of business failure.
This finding supports the debate on the diversity of corporate governance structures, and particularly the role of pressure-resistant shareholders in the avoidance of the firm's financial distress.
We have synthesised and characterised the complex Ni(tpy)
(tpy = 2,2':6',2''-terpyridine). This formally Ni(0) complex is paramagnetic both in the solid state and in solution (
= 2). The crystal ...structure shows an octahedral geometry, with molecules arranged in independent dimers involving π-stacking between pairs of complexes. Magnetic measurementes and DFT calculations suggest the existence of temperature-dependent intermolecular antiferromagnetic coupling in the solid state.
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