PURPOSE OF REVIEWThe objective of this review is to provide an update on our evolving understanding of the effects of stress in pregnancy and during early development on the onset of asthma-related ...phenotypes across childhood, adolescence, and into early adulthood.
RECENT FINDINGSAccumulating evidence over the past 2 decades has established that prenatal and early-life psychological stress and stress correlates (e.g., maternal anxiety or depression) increase the risk for childhood respiratory disorders. Recent systematic reviews and meta-analyses including numerous prospective epidemiological and case–control studies substantiate a significant effect of prenatal stress and stress in early childhood on the development of wheeze, asthma, and other atopic-related disorders (eczema and allergic rhinitis), with many studies showing an exposure–response relationship. Offspring of both sexes are susceptible to perinatal stress, but effects differ. The impact of stress on child wheeze/asthma can also be modified by exposure timing. Moreover, coexposure to prenatal stress can enhance the effect of chemical stressors, such as prenatal traffic-related air pollution, on childhood respiratory disease risk. Understanding complex interactions among exposure dose, timing, child sex, and concurrent environmental exposures promises to more fully characterize stress effects and identify susceptible subgroups. Although the link between perinatal stress and childhood asthma-related phenotypes is now well established, pathways by which stress predisposes children to chronic respiratory disorders are not as well delineated. Mechanisms central to the pathophysiology of wheeze/asthma and lung growth and development overlap and involve a cascade of events that include disrupted immune, neuroendocrine, and autonomic function as well as oxidative stress. Altered homeostatic functioning of these integrated systems during development can enhance vulnerability to asthma and altered lung development.
SUMMARYMechanistic studies that more comprehensively assess biomarkers reflecting alterations across interrelated stress response systems and associated regulatory processes, in both pregnant women and young children, could be highly informative. Leveraging high-throughput systems-wide technologies to include epigenomics (e.g., DNA methylation, microRNAs), transcriptomics, and microbiomics as well as integrated multiomics are needed to advance this field of science. Understanding stress-induced physiological changes occurring during vulnerable life periods that contribute to chronic respiratory disease risk could lead to the development of preventive strategies and novel therapeutic interventions.
The allocation of deceased donor kidneys has become more complex because of the increasing spectrum of donors and recipients age and comorbidities. Several scoring systems have been proposed to ...evaluate the donor quality of deceased donor kidneys, based on clinical, pathological or combined parameters to predict the risk of renal allograft failure. Nonetheless, besides the dichotomous extended criteria donor (ECD) score, none of the others have been used in clinical practice because of numerous reasons, ranging from lack of robust validation to the technical challenges associated with the evaluation of donor biopsies. Recently, the Kidney Donor Risk Index (KDRI) and Profile Index (KDPI) were introduced in the USA as a refined version of the ECD score. This scoring system is based on 10 donor factors, therefore providing a finely granulated evaluation of donor quality without the need of a kidney biopsy.Here, we review the advantages and drawbacks of the main scoring systems, and we describe the components of the KDRI and KDPI. It is an easily accessible online tool, based solely on donor factors readily available at the moment of the donor offer. Importantly, the KDPI has also been made part of the 'longevity matching' allocation in the USA, where the best kidneys are allocated to the recipients with the longest predicted post-transplant survival. The KDRI should provide us with a robust qualitative evaluation of deceased donor quality, and therefore will probably play a role in deceased donor kidney allocation policies across Europe in the near future. Hopefully, the KDRI and the KDPI should help transplant programmes to better allocate the scarce resource of deceased donor kidneys.
The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and ...difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A cryo-electron microscopy structure of HexaPro at a resolution of 3.2 angstroms confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Kaali et al. discuss the paper by Checkley and colleagues which examines the effect of a year-long, multifaceted liquefied petroleum gas (LPG) cookstove intervention as compared with biomass ...(commonly animal dung) cookstove on cardiopulmonary health in adults, specifically resting BP, peak expiratory flow (PEF), and respiratory symptoms as measured by the St. George's Respiratory Questionnaire. The primary finding of this impressive study was that a year-long LPG intervention with robust measures to enable LPG stove use was not associated with improvement in BP, PEF, or respiratory symptoms in women randomized to the cleaner burning LPG stove as compared with control. Strikingly, exposure-response analyses found no association between average personal PM2.5 exposure and systolic or diastolic BP or postbronchodilator PEF (but did suggest that higher personal PM2.5 exposure was associated with lower prebronchodilator PEF).
It is obvious why it is important to cut air pollution levels: doing so will improve public health and have a positive impact on climate action. The American Thoracic Society (ATS), the foremost ...medical organization dedicated to improving respiratory health worldwide, has a duty to promote protective air quality standards that take into account the most recent findings in scientific research regarding the dangers of exposure to outdoor pollution. The United States (U.S.), also known as the U.S. According to the Clean Air Act, the Environmental Protection Agency (EPA) Administrator is in charge of making final decisions about the National Ambient Air Quality Standards (NAAQS) for fine particulate matter (PM2.5). Technical and policy documentation created by EPA staff under the direction of are a significant help in making this decision.
Reshaping Doctoral Education Lee, Alison; Danby, Susan
Routledge, Taylor & Francis Group,
2012, 20120312, 2011-12-02
eBook, Book
The number of doctorates being awarded around the world has almost doubled over the last ten years, propelling it from a small elite enterprise into a large and ever growing international market. ...Within the context of increasing numbers of doctoral students this book examines the new doctorate environment and the challenges it is starting to face. Drawing on research from around the world the individual authors contribute to a previously under-represented focus of theorising the emerging practices of doctoral education and the shape of change in this arena.
Key aspects, expertly discussed by contributors from the UK, USA, Australia, New Zealand, China, South Africa, Sweden and Denmark include:
the changing nature of doctoral education
the need for systematic and principled accounts of doctoral pedagogies
the importance of disciplinary specificity
the relationship between pedagogy and knowledge generation
issues of transdisciplinarity.
Reshaping Doctoral Education provides rich accounts of traditional and more innovative pedagogical practices within a range of doctoral systems in different disciplines, professional fields and geographical locations, providing the reader with a trustworthy and scholarly platform from which to design the doctioral experience. It will prove an essential resource for anyone involved in doctorate studies, whether as students, supervisors, researchers, administrators, teachers or mentors.
Some patients with coronavirus disease (COVID-19) pneumonia demonstrate severe hypoxemia despite having near normal lung compliance, a combination not commonly seen in typical acute respiratory ...distress syndrome (ARDS). The disconnect between gas exchange and lung mechanics in COVID-19 pneumonia has raised the question of whether the mechanisms of hypoxemia in COVID-19 pneumonia differ from those in classical ARDS. Dual-energy computed tomographic imaging has demonstrated pulmonary vessel dilatation and autopsies have shown pulmonary capillary deformation in patients with COVID-19 pneumonia. These data suggest that pulmonary vasodilatations may explain the disproportionate hypoxemia in some patients with COVID-19 pneumonia and, somewhat surprisingly, track with poor lung compliance. Our detection of transpulmonary bubbles may be analogous to hepatopulmonary syndrome, a pulmonary vascular disorder of chronic liver disease characterized by pulmonary vascular dilatations with increased blood flow to affected lung units, which results in ventilation-perfusion mismatch and hypoxemia. The normal lung filters microbubbles from the injection of agitated saline as the bubble diameter is larger.
Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the ...sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.
Cyclostomes, comprising jawless vertebrates such as lampreys and hagfishes, are the sister group of living jawed vertebrates (gnathostomes) and hence an important group for understanding the origin ...and diversity of vertebrates. In vertebrates and other metazoans, Hox genes determine cell fate along the anteroposterior axis of embryos and are implicated in driving morphological diversity. Invertebrates contain a single Hox cluster (either intact or fragmented), whereas elephant shark, coelacanth, and tetrapods contain four Hox clusters owing to two rounds of whole-genome duplication (“1R” and “2R”) during early vertebrate evolution. By contrast, most teleost fishes contain up to eight Hox clusters because of an additional “teleost-specific” genome duplication event. By sequencing bacterial artificial chromosome (BAC) clones and the whole genome, here we provide evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). This suggests that the lamprey lineage has experienced an additional genome duplication after 1R and 2R. The relative age of lamprey and human paralogs supports this hypothesis. Compared with gnathostome Hox clusters, lamprey Hox clusters are unusually large. Several conserved noncoding elements (CNEs) were predicted in the Hox clusters of lamprey, elephant shark, and human. Transgenic zebrafish assay indicated the potential of CNEs to function as enhancers. Interestingly, CNEs in individual lamprey Hox clusters are frequently conserved in multiple Hox clusters in elephant shark and human, implying a many-to-many orthology relationship between lamprey and gnathostome Hox clusters. Such a relationship suggests that the first two rounds of genome duplication may have occurred independently in the lamprey and gnathostome lineages.
Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human‐like post‐translational ...modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO‐K1, CHO‐DXB11, and CHO‐DG44) in suspension cultures and further report their growth‐related characteristics, and N‐ and O‐glycosylation patterns of host cell proteins (HCPs). The comparative multi‐omics and subsequent genome‐scale metabolic network model‐based enrichment analyses indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell‐cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N‐ and O‐glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced.
A mammalian systems biotechnology approach exploited multi‐omics profiles together with genome‐scale metabolic network model to systematically link the possible phenotypic differences across Chinese hamster ovary (CHO) host cell lines with their genotypes. The current work highlights that the genetic diversity and heterogeneity of CHO cells indeed affect their growth phenotype as well as glycosylation patterns, thus serving as a good starting point for the rational selection of relevant CHO host cells as well as to establish cell line engineering targets.
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