Novel unexpected functions of PHA granules Obruca, Stanislav; Sedlacek, Petr; Slaninova, Eva ...
Applied microbiology and biotechnology,
06/2020, Letnik:
104, Številka:
11
Journal Article
Recenzirano
Polyhydroxyalkanoates (PHA), polyesters accumulated by numerous prokaryotes in the form of intracellular granules, have been for decades considered being predominantly storage molecules. However, ...numerous recent discoveries revealed and emphasized their complex biological role for microbial cells. Most of all, it was repeatedly reported and confirmed that the presence of PHA granules in prokaryotic cells enhances stress resistance and robustness of microbes against various environmental stress factors such as high or low temperature, freezing, oxidative, and osmotic pressure. It seems that protective mechanisms of PHA granules are associated with their extraordinary architecture and biophysical properties as well as with the complex and deeply interconnected nature of PHA metabolism. Therefore, this review aims at describing novel and unexpected properties of PHA granules with respect to their contribution to stress tolerance of various prokaryotes including common mesophilic heterotrophic bacteria, but also extremophiles or photo-autotrophic cyanobacteria.
Key points
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PHA granules present in bacterial cells reveal unique properties and functions.
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PHA enhances stress robustness of bacterial cells.
The study deals with the land register of the town of Boskovice, inventory no. 44 (1784–1790), from the paleographic point of view. It especially focuses on the handwriting identification of the ...scribes that participated in its functioning in the 18th century. In addition to elementary questions about determining the style of writing and the way of using abbreviations, it tries to observe possible integration of humanistic elements into neo-Gothic cursive (“Kurrent”).
The research aim was to use orange essential oil and trehalose in a carrageenan matrix to form edible packaging. The edible packaging experimentally produced by casting from an aqueous solution were ...evaluated by the following analysis: UV-Vis spectrum, transparency value, transmittance, attenuated total reflectance Fourier-Transform spectroscopy (FTIR), scanning electron microscopy (SEM) and antimicrobial activity. The obtained results showed that the combination of orange essential oil with trehalose decreases the transmittance value in the UV and Vis regions (up to 0.14% ± 0.02% at 356 nm), meaning that produced films can act as a UV protector. Most produced films in the research were resistant to Gram-positive bacteria (
subsp.
), though most films did not show antibacterial properties against Gram-negative bacteria and yeasts. FTIR and SEM confirmed that both the amount of carrageenan used and the combination with orange essential oil influenced the compatibility of trehalose with the film matrix. The research showed how different combinations of trehalose, orange essential oils and carrageenan can affect edible film properties. These changes represent important information for further research and the possible practical application of these edible matrices.
Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects ...are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.
FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).
Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95;
< .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17;
< .0001) and 0.02 (95% CI, < 0.01 to 0.05;
= .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.
Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
This paper shows that employment in cohorts of US firms is strongly influenced by aggregate conditions at the time of their entry. Employment fluctuations of startups are procyclical, they persist ...into later years, and cohort-level employment variations are largely driven by differences in firm size, rather than the number of firms. An estimated general equilibrium firm dynamics model reveals that aggregate conditions at birth, rather than post-entry choices, drive the majority of cohort-level employment variation by affecting the share of startups with high growth potential. In the aggregate, changes in startup conditions result in large, slow-moving fluctuations in employment.
Humic acids are often regarded as substances with a supramolecular structure which plays an important role in Nature. Their addition into hydrogels can affect their behavior and functioning in ...different applications. This work is focused on the properties of widely-used hydrogel based on agarose after addition of humic acids-the protonated H-form of humic acids and humic acids with methylated carboxylic groups. Hydrogels enriched by humic acids were studied in terms of their viscoelastic and transport properties. Rotational rheometry and methods employing diffusion cells were used in order to describe the influence of humic acids on the properties and behavior of hydrogels. From the point of view of rheology the addition of humic acids mainly affected the loss modulus corresponding to the relaxation of hydrogel connected with its flow. In the case of diffusion experiments, the transport of dyes (methylene blue and rhodamine) and metal ions (copper and nickel) through the hydrogel was affected by interactions between humic acids and the diffusion probes. The time lag in the hydrogel enriched by humic acids was prolonged for copper, methylene blue and rhodamine. In contrast, the presence of humic acids in hydrogel slightly increased the mobility of nickel. The strongest influence of the methylation of humic acids on diffusion was observed for methylene blue.
Accumulation of polyhydroxybutyrate (PHB) seems to be a common metabolic strategy adopted by many bacteria to cope with cold environments. This work aimed at evaluating and understanding the ...cryoprotective effect of PHB. At first a monomer of PHB, 3-hydroxybutyrate, was identified as a potent cryoprotectant capable of protecting model enzyme (lipase), yeast (Saccharomyces cerevisiae) and bacterial cells (Cupriavidus necator) against the adverse effects of freezing-thawing cycles. Further, the viability of the frozen-thawed PHB accumulating strain of C. necator was compared to that of the PHB non-accumulating mutant. The presence of PHB granules in cells was revealed to be a significant advantage during freezing. This might be attributed to the higher intracellular level of 3-hydroxybutyrate in PHB accumulating cells (due to the action of parallel PHB synthesis and degradation, the so-called PHB cycle), but the cryoprotective effect of PHB granules seems to be more complex. Since intracellular PHB granules retain highly flexible properties even at extremely low temperatures (observed by cryo-SEM), it can be expected that PHB granules protect cells against injury from extracellular ice. Finally, thermal analysis indicates that PHB-containing cells exhibit a higher rate of transmembrane water transport, which protects cells against the formation of intracellular ice which usually has fatal consequences.
•Firm entry dropped in unprecedented fashion in the U.S. during the Great Recession.•This paper develops a search and matching model with firm dynamics.•A lost generation of firms has limited impact ...in the short run.•Incumbent firms hire more unemployed and workers hang on to their jobs more.•Nevertheless, a lost generation of firms leaves a persistent employment dent.
Can the unprecedented lack of startups during the U.S. Great Recession have persistently negative effects? While fewer firms hiring workers can mechanically reduce employment for many years, this may be offset by feedback effects on lower wages, slacker labor markets and higher profits. An estimated model of firm dynamics and frictional labor markets suggests that such feedback effects are too weak to offset the direct impact of fewer startups. Had firm entry remained constant during the Great Recession, output would have recovered 4–6 years earlier and unemployment would have been 0.5 percentage points lower even 10 years after the crisis.
Inborn errors of immunity are genetic disorders characterized by various degrees of immune dysregulation that can manifest as immune deficiency, autoimmunity, or autoinflammation. The routine use of ...next-generation sequencing in the clinic has facilitated the identification of an ever-increasing number of inborn errors of immunity, revealing the roles of immunologically important genes in human pathologies. However, despite this progress, treatment is still extremely challenging.
We sought to report a new monogenic autoinflammatory disorder caused by a de novo activating mutation, p.Tyr515∗, in hematopoietic cell kinase (HCK). The disease is characterized by cutaneous vasculitis and chronic pulmonary inflammation that progresses to fibrosis.
Whole-exome sequencing, Sanger sequencing, mass spectrometry, and western blotting were performed to identify and characterize the pathogenic HCK mutation. Dysregulation of mutant HCK was confirmed ex vivo in primary cells and in vitro in transduced cell lines.
Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 exhibited increased kinase activity and enhanced myeloid cell priming, migration and effector functions, such as production of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, and production of reactive oxygen species. These aberrant functions were reflected by inflammatory leukocyte infiltration of the lungs and skin. Moreover, an overview of the clinical course of the disease, including therapies, provides evidence for the therapeutic efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in inflammatory lung disease.
We propose HCK-driven pulmonary and cutaneous vasculitis as a novel autoinflammatory disorder of inborn errors of immunity.
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