Abstract
Among the investigated mechanisms of chemotherapy-induced damage to human primordial follicle reserve are induction of DNA double-strand breaks (DSBs) and resultant apoptotic death, ...stromal–microvascular damage and follicle activation. Accumulating basic and translational evidence suggests that acute exposure to gonadotoxic chemotherapeutics, such as cyclophosphamide or doxorubicin, induces DNA DSBs and triggers apoptotic death of primordial follicle oocytes within 12–24 h, resulting in the massive loss of ovarian reserve. Evidence also indicates that chemotherapeutic agents can cause microvascular and stromal damage, induce hypoxia and indirectly affect ovarian reserve. While it is possible that the acute reduction of the primordial follicle reserve by massive apoptotic losses may result in delayed activation of some primordial follicles, this is unlikely to be a predominant mechanism of loss in humans. Here, we review these mechanisms of chemotherapy-induced ovarian reserve depletion and the potential reasons for the discrepancies among the studies. Based on the current literature, we propose an integrated hypothesis that explains both the acute and delayed chemotherapy-induced loss of primordial follicle reserve in the human ovary.
Uterus transplantation is an experimental infertility treatment for women with uterine factor infertility. During donor uterus retrieval and subsequent storage, ischemia and other stressors are ...likely to occur, resulting in the delayed restoration of organ function and increased graft rejection. The uterus expresses connexin-based hemichannels, the opening of which can promote ischemic cell death, as well as gap junctions that may expand cell death by bystander signaling. We investigated if connexin channel inhibition with connexin channel inhibitor Gap27 could protect the uterus against cell death during the storage period. The study involved 9 female patients undergoing gender-change surgery. Before uterus removal, it was exposed to in situ warm ischemia with or without reperfusion. Uterus biopsies were taken before, during, and after ischemia, with or without reperfusion, and were subsequently stored under cold (4ᵒC) or warm (37ᵒC) conditions. TUNEL cell death assay was done at various time points along the combined in vivo/ex vivo experimental timeline. We found that Gap27 protected against storage-related cell death under cold but not warm conditions when the uterus had experienced in situ ischemia/reperfusion. For in situ brief ischemia without reperfusion, Gap27 reduction of cell death was delayed and significantly less, suggesting that protection critically depends on processes initiated when the organ was still in the donor. Thus, the inclusion of the connexin channel inhibitor Gap27 during cold storage protects the uterus against cell death, and the degree of protection depends on the history of exposure to warm ischemia. Gap27 protection may be indicated for uteri from deceased donors, in which ischemia is likely because life-saving organs have retrieval priority.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Limiting the emission of pollutants, including carbon dioxide, to the atmosphere has recently become an important element of global energy policy. This policy is a result of new and existing ...commitments, such as the Energy–Climate Package and the Emission Trading Scheme, introduced by Directive 2009/29/EC. These obligations impose the requirement for a significant reduction of CO2 emissions from power generation processes on the member countries of the European Union. Such reduction is a difficult task, especially in countries in which the share of coal in the electricity generation process is significant. There are several methods for the reduction of emissions from energy production processes. One of the methods of increasing the efficiency of power systems is to increase the steam parameters. However, limiting emissions only by increasing the efficiency of energy production is not always sufficient. Thus, it is important to consider the implementation of carbon-dioxide-capture installations in supercritical power plants. The greatest disadvantage of existing separation methods is the high-energy requirements of the capture processes. In the case of amine-based chemical absorption, this requirement causes a decrease of the efficiency of the electricity production process by even as much as 10 percentage points. Therefore, new methods of CO2 capture are required that will allow for the reduction of the energy consumption of the process. In this paper, the two methods of post-combustion carbon dioxide capture from the flue gas of an ultra-supercritical coal unit are described and the processes are compared. The selected methods are chemical absorption with the use of an aqueous solution of monoethanolamine (MEA) and membrane separation with the use of ceramic–polymer membranes that have an ideal selectivity coefficient equal to 100. To conduct these analyses, adequate models of the systems were built in the Aspen Plus software. A comparison of these methods was made primarily from the perspective of the energy intensity of the particular processes, but also the possibility of decreasing the energy intensity of that process was applied. The calculations for the separation process were made in such a way as to obtain the same CO2-purity and CO2-capture rate levels. The results of this analysis show that, in terms of energy intensity, both separation processes perform at a similar level, although the performance of membranes is slightly better. When the compression process of the captured CO2 before transport to a storage place is considered, the absorption process is significantly less energy-intensive than membrane separation. However, the development of membrane techniques allows for the assumption that this technology could be competitive with other separation methods in the future, especially from the perspective of effectiveness and cost.
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IJS, KILJ, NUK, PNG, UL, UM
Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal ...disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31
mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31
mouse retinae and RPE. Mis-splicing of genes implicated in ciliogenesis and cellular adhesion was associated with severe RPE defects that include disrupted apical - basal polarity, reduced trans-epithelial resistance and phagocytic capacity, and decreased cilia length and incidence. Disrupted cilia morphology also occurred in patient-derived photoreceptors, associated with progressive degeneration and cellular stress. In situ gene editing of a pathogenic mutation rescued protein expression and key cellular phenotypes in RPE and photoreceptors, providing proof of concept for future therapeutic strategies.
In response to salinity and various other environmental stresses, plants accumulate reactive oxygen species (ROS). The ROS produced at very early stages of the stress response act as signaling ...molecules activating defense mechanisms, whereas those produced at later stages in an uncontrolled way are detrimental to plant cells by damaging lipids, DNA, and proteins. Multiple systems are involved in ROS generation and also in ROS scavenging. Their level and activity are tightly controlled to ensure ROS homeostasis and protect the plant against the negative effects of the environment. The signaling pathways responsible for maintaining ROS homeostasis in abiotic stress conditions remain largely unknown. Here, we show that in
, two abscisic acid- (ABA)-non-activated SNF1-releted protein kinases 2 (SnRK2) kinases, SnRK2.4 and SnRK2.10, are involved in the regulation of ROS homeostasis in response to salinity. They regulate the expression of several genes responsible for ROS generation at early stages of the stress response as well as those responsible for their removal. Moreover, the SnRK2.4 regulate catalase levels and its activity and the level of ascorbate in seedlings exposed to salt stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this paper the thermo-economic analysis of the oxy-type supercritical power plant integrated with the cryogenic air separation unit was presented, with the efficiency of the whole power plant of ...32.26%. The reduction of energy intensity of ASU (air separation unit) was proposed by appending the membrane module. A hybrid air separation unit allows to decrease the energy intensity of oxygen production from the value of 0.226 kWh/kg O2 for the cryogenic ASU to 0.179 kWh/kg O2, for the analyzed hybrid membrane-cryogenic ASU, with an increase of the net efficiency to 33.84%. This solution causes the efficiency change by 8.7 percentage points in comparison with the reference air-fired power plant.
A method of using the waste heat from the ASU and CCS (CO2 capture system) installations for the regeneration system of the steam turbine was proposed as a mean to decrease the efficiency drop. Using the waste heat in the steam turbine system causes an increase of the electric energy of the generator of turbine, and in the consequence leads to the improvement of the efficiency of the analyzed power plant by 0.5 percentage points. An economic analysis showed that the profitability of building of the oxy-type power plant in place of a conventional power plant will be higher with the price of CO2 emission allowances equal to 27.1 €/Mg CO2. All these effects of increasing the efficiency of the block can lead to lowering the cost of electricity generation by 5 €/MWh.
•Comparison of net efficiency in the analyzed oxy and air power plant.•Analysis of possibilities of increase the power plant net efficiency.•Increase the boiler thermal efficiency by change of flue gas recirculation method.•Analysis of using the low-temperature heat from ASU and CCS installations.•Economic analysis of the analyzed power plant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
SNF1‐related protein kinases 2 (SnRK2s) regulate the plant responses to abiotic stresses, especially water deficits. They are activated in plants subjected to osmotic stress, and some of them are ...additionally activated in response to enhanced concentrations of abscisic acid (ABA) in plant cells. The SnRK2s that are activated in response to ABA are key elements of ABA signalling that regulate plant acclimation to environmental stresses and ABA‐dependent development. Much less is known about the SnRK2s that are not activated by ABA, albeit several studies have shown that these kinases are also involved in response to osmotic stress. Here, we show that one of the Arabidopsis thaliana ABA‐non‐activated SnRK2s, SnRK2.10, regulates not only the response to salinity but also the plant sensitivity to dehydration. Several potential SnRK2.10 targets phosphorylated in response to stress were identified by a phosphoproteomic approach, including the dehydrins ERD10 and ERD14. Their phosphorylation by SnRK2.10 was confirmed in vitro. Our data suggest that the phosphorylation of ERD14 within the S‐segment is involved in the regulation of dehydrin subcellular localization in response to stress.
The ABA‐non‐activated SNF1‐related protein kinases 2 (SnRK2s) are strongly activated in the plant response to water deficits and salinity; however, information concerning their roles in the response to stress is limited. Using a phosphoproteomic approach, we identified several potential targets of one kinase of this group, SnRK2.10, that are phosphorylated in response to salt stress. Our data showed that two dehydrins, ERD10 and ERD14, are phosphorylated by SnRK2.10 in vivo and in vitro and suggested that the phosphorylation of ERD14 within the S‐segment is involved in the regulation of its subcellular localization in response to stress.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our ...knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete.
We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their "mutation load" beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population.
Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies.
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