The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 ...(SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.
Oral budesonide is a second‐generation steroid that allows local, selective treatment of the gastrointestinal tract and the liver, minimizing systemic exposure. The results of randomized trials ...comparing budesonide versus placebo or active comparators have led to expert recommendations that budesonide be used to treat mild or moderate active ileocecal Crohn's disease, microscopic colitis (including both collagenous and lymphocytic colitis), ulcerative colitis, and non‐cirrhotic autoimmune hepatitis. The mechanism of budesonide action obviates the need for dose tapering due to safety reasons after induction therapy. Where low‐dose budesonide is used to maintain remission, usually in microscopic colitis, it does not appear to have adverse safety implications other than slight reductions in cortisol levels on rare occasions. As a gut‐selective and liver‐selective corticosteroid, budesonide offers an appealing alternative to conventional systemic glucocorticoids in diseases of these organs.
Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system ...activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function.
Coenzyme Q biosynthesis in health and disease Acosta, Manuel Jesús; Vazquez Fonseca, Luis; Desbats, Maria Andrea ...
Biochimica et biophysica acta,
August 2016, 2016-Aug, 2016-08-00, Letnik:
1857, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Coenzyme Q (CoQ, or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is ...also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant.
CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ, but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7.
Mutations in human COQ genes cause primary CoQ10 deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy.
The pathogenesis of CoQ10 deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ10 function are implicated.
CoQ10 deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQ10 supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled ‘EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2–6, 2016’, edited by Prof. Paolo Bernardi.
•Coenzyme Q is an essential component of the mitochondrial respiratory chain and an antioxidant.•Its biosynthesis requires a set of at least 12 proteins encoded by COQ genes.•These proteins form a complex localized to the inner mitochondrial membrane.•Mutations in COQ genes cause primary CoQ10 deficiency.•Many patients with CoQ10 deficiency respond to oral CoQ10 supplementation.
Adventitious root (AR) formation in excised plant parts is a bottleneck for survival of isolated plant fragments. AR formation plays an important ecological role and is a critical process in cuttings ...for the clonal propagation of horticultural and forestry crops. Therefore, understanding the regulation of excision-induced AR formation is essential for sustainable and efficient utilization of plant genetic resources.
Recent studies of plant transcriptomes, proteomes and metabolomes, and the use of mutants and transgenic lines have significantly expanded our knowledge concerning excision-induced AR formation. Here, we integrate new findings regarding AR formation in the cuttings of diverse plant species. These findings support a new system-oriented concept that the phytohormone-controlled reprogramming and differentiation of particular responsive cells in the cutting base interacts with a co-ordinated reallocation of plant resources within the whole cutting to initiate and drive excision-induced AR formation. Master control by auxin involves diverse transcription factors and mechanically sensitive microtubules, and is further linked to ethylene, jasmonates, cytokinins and strigolactones. Hormone functions seem to involve epigenetic factors and cross-talk with metabolic signals, reflecting the nutrient status of the cutting. By affecting distinct physiological units in the cutting, environmental factors such as light, nitrogen and iron modify the implementation of the genetically controlled root developmental programme.
Despite advanced research in the last decade, important questions remain open for future investigations on excision-induced AR formation. These concern the distinct roles and interactions of certain molecular, hormonal and metabolic factors, as well as the functional equilibrium of the whole cutting in a complex environment. Starting from model plants, cell type- and phase-specific monitoring of controlling processes and modification of gene expression are promising methodologies that, however, need to be integrated into a coherent model of the whole system, before research findings can be translated to other crops.
LINKED CONTENT
This article is linked to Fukuda et al papers. To view these articles, visit https://doi.org/10.1111/apt.18013 and https://doi.org/10.1111/apt.18111
Ante la actual crisis natural y humana, la filosofía ambiental surge como un saber complejo y un repensar, que aborda principalmente la interrelación humano–naturaleza y la búsqueda de la convivencia ...con sentido de equilibrio en la Tierra. En ese contexto, el objetivo del presente artículo es reflexionar sobre los aportes de Arne Naess, Ricardo Rozzi y Leonardo Boff ¿En qué medida los autores contribuyen al desarrollo de la filosofía ambiental? Los métodos utilizados son la recopilación documental y la hermenéutica analógica. Como resultado, se encuentra que Naess introduce la idea de buscar un equilibrio y florecimiento de la vida; por su parte, Rozzi propone una filosofía ambiental de campo y una nueva ética biocultural, y Boff complementa con la idea del cuidado esencial. Se concluye que, en conjunto, los tres filósofos contribuyen al nacimiento y al enriquecimiento de la filosofía ambiental como un nuevo campo de reflexión y acción filosófica que se centra en el fluir del sistema vida.
Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program ...training environments are also marked by structural barriers that negatively impact measurable academic outcomes of underrepresented and/or marginalized students in academic medicine (racial and ethnic minority groups considered underrepresented by the National Institute of Health, sexual and gender minorities, individuals with disabilities, and individuals of low socioeconomic status). In this article, we review the existing literature on MD-PhD program disparities affecting students from these groups and provide recommendations grounded on the reviewed evidence. Our literature review identified four generalizable barriers that can impact the training outcomes of students from these marginalized and/or underrepresented groups: 1) discrimination and bias, 2) impostor syndrome and stereotype threat, 3) lack of identity-similar mentors, and 4) suboptimal institutional policies and procedures. We propose goal-oriented interventions that may begin to ameliorate the disparities present in MD-PhD program training environments that affect students from marginalized and/or underrepresented groups in academic medicine.
In this paper, a review on road friction virtual sensing approaches is provided. In particular, this work attempts to address whether the road grip potential can be estimated accurately under regular ...driving conditions in which the vehicle responses remain within low longitudinal and lateral excitation levels. This review covers in detail the most relevant effect-based estimation methods; these are methods in which the road friction characteristics are inferred from the tyre responses: tyre slip, tyre vibration, and tyre noise. Slip-based approaches (longitudinal dynamics, lateral dynamics, and tyre self-alignment moment) are covered in the first part of the review, while low frequency and high frequency vibration-based works are presented in the following sections. Finally, a brief summary containing the main advantages and drawbacks derived from each estimation method and the future envisaged research lines are presented in the last sections of the paper.
Background
An increasing number of reports have described the COVID‐19–associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus ...statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA.
Methods
We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID‐19 laboratory‐confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case.
Results
Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases.
Conclusion
We found a high frequency of proven CAPA among patients with severe COVID‐19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.
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