Search

The placenta, a pivotal organ in mammalian reproduction, allows nutrient exchange and hormonal signaling between the mother and the developing fetus. Understanding its molecular intricacies is essential for deciphering normal embryonic development and pathological conditions such as tumorigenesis. Here, we explore the multifaceted role of the tumor suppressor BRCA1-associated protein 1 (BAP1) in cancer and placentation. Initially recognized for its tumor-suppressive properties, BAP1 has emerged as a key regulator at the intersection of tumorigenesis and placental development. BAP1 influences crucial cellular processes such as cell death, proliferation, metabolism, and response to hypoxic conditions. By integrating insights from tumor and developmental biology, we illuminate the complex molecular pathways orchestrated by BAP1. This perspective highlights BAP1's significant impact on both cancer and placental development, and suggests novel therapeutic strategies that could improve outcomes for pregnancy disorders and cancer. This perspective explores the dual role of the tumor suppressor BAP1 in placental development and cancer. By integrating insights from tumor and developmental biology, the study offers new therapeutic targets for pregnancy disorders and cancer. [ABSTRACT FROM AUTHOR]

The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the differentiation of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSCs) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups, suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions. [ABSTRACT FROM AUTHOR]

This study proposes the experimental evaluation of alternative refrigerants with low global warming potentials (GWPs) such as R1234ze(E), R513A, and the mixture R516A as a drop-in replacement for R134a in a domestic refrigerator with a volumetric capacity of 513 L. Initially, the optimal charge for each refrigerant was defined based on the minimum energy consumption of the refrigerator, then the thermal and energy performance of the refrigerator was evaluated. Finally, a total equivalent warming impact analysis (TEWI) was performed. The main results indicated that the optimal charge of the alternative refrigerants was below that corresponding to R134a (105 g), of which R516A (86 g) presented the greatest charge reduction. Regarding the average temperature of the refrigerator compartments, very adequate thermal conditions were observed; thus, the alternative refrigerants showed very similar conditions to R134a. For the coefficient of performance (COP) and considering R134a as a reference, it was observed that R513A presented the greatest reduction of around 28%, while R1234ze(E) showed an increase of 13% in relation to R134a. Finally, the TEWI analysis showed R1234ze(E) as the refrigerant with the least impact. [ABSTRACT FROM AUTHOR]

Global polystyrene (PS) production has been influenced by the lightness and heat resistance this material offers in different applications, such as construction and packaging. However, population growth and the lack of PS recycling lead to a large waste generation, affecting the environment. Pyrolysis has been recognized as an effective recycling method, converting PS waste into valuable products in the chemical industry. The present work addresses a systematic, bibliometric, and statistical analysis of results carried out from 2015 to 2022, making an extensive critique of the most influential operation parameters in the thermo-catalytic pyrolysis of PS and its waste. The systematic study showed that the conversion of PS into a liquid with high aromatic content (84.75% of styrene) can be achieved by pyrolysis. Discussion of PS as fuel is described compared to commercial fuels. In addition, PS favors the production of liquid fuel when subjected to co-pyrolysis with biomass, improving its properties such as viscosity and energy content. A statistical analysis of the data compilation was also discussed, evaluating the influence of temperature, reactor design, and catalysts on product yield. [ABSTRACT FROM AUTHOR]

This study presents the optimization of a multilayer wire-on-tube condenser exposed to forced convection, using the Optimized Multi-objective Particle Swarm Optimization (OMOPSO) algorithm. The maximization of the heat transfer and the minimization of the heat exchange area were defined as objective functions. In the optimization process, the variations of eight geometric parameters of the condenser were analyzed, and the Multi-objective Evolutionary Algorithm based on Decomposition (MOEAD), Non-dominated Sorting Genetic Algorithm-II (NSGAII), and OMOPSO algorithms were statistically explored. Furthermore, the condenser optimization analysis was extended to the use of alternative refrigerants to R134a such as R600a and R513A. Among the relevant results, it can be commented that the OMOPSO algorithm presented the best option from the statistical point of view compared to the other two algorithms. Thus, optimal designs for the wire-on-tube condenser were defined for three proposed study cases and for each refrigerant, providing an overview of compact designs. Likewise, the reduction of the condenser area was analyzed in more detail, presenting a maximum reduction of 15% for the use of R134a compared to for the current design. Finally, the crossflow condition was studied with respect to the current one, concluding in a greater heat transfer and a smaller heat exchange surface. [ABSTRACT FROM AUTHOR]

The use of an internal heat exchanger in vapor compression refrigeration systems of one stage is a common practice because it helps to increase the cooling capacity in the evaporator. Furthermore, the use of refrigerants with low global warming potential is becoming more frequent due to environmental regulations worldwide. Thus, this paper presents an evaluation of the improvement produced by the inclusion of an internal heat exchanger cycle (IHXC) in an experimental installation from the viewpoint of exergy, economic and environmental through to exergy, exergoeconomics, and Specific Life Cycle Climate Performance (SLCCP) studies. The tests were conducted using R1234ze(E) as a replacement alternative to R134a in three evaporating temperature conditions: 4 °C, 9 °C, and 14 °C. Comparisons were made considering R134a in BRC mode versus R1234ze(E) in BRC and IHXC modes. Results show that a lower environmental impact is produced by an evaporating temperature of 14 °C with a reduction in SLCCP of 13.3% using IHXC and R1234ze(E). Moreover, the highest increase in exergy efficiency was observed for an evaporating temperature of 4 °C, with this increase being 9%, while the lowest increase in the total cost rate was observed for the same evaporating temperature, being 12.3% and 21.2% for BRC and IHXC modes using R1234ze(E), respectively. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) channels play prominent roles in ion homeostasis by their ability to control cation influx. Mouse placentation is governed by the processes of trophoblast proliferation, invasion, differentiation, and fusion, all of which require calcium signaling. Although certain TRP channels have been shown to contribute to maternal–fetal transport of magnesium and calcium, a role for TRP channels in specific trophoblast functions has been disregarded. Using qRT-PCR and in situ hybridisation, the spatio-temporal expression pattern of TRP channels in the mouse placenta across gestation (E10.5–E18.5) was assessed. Prominent expression was observed for Trpv2, Trpm6, and Trpm7. Calcium microfluorimetry in primary trophoblast cells isolated at E14.5 of gestation further revealed the functional activity of TRPV2 and TRPM7. Finally, comparing TRP channels expression in mouse trophoblast stem cells (mTSCs) and mouse embryonic stem cells (mESC) confirmed the specific expression of TRPV2 during placental development. Moreover, TRP channel expression was similar in mTSCs compared to primary trophoblasts and validate mTSC as a model to study TRP channels in placental development. Collectivity, our results identify a specific spatio-temporal TRP channel expression pattern in trophoblasts, suggesting a possible involvement in regulating the process of placentation. [ABSTRACT FROM AUTHOR]

Transient behavior of internal heat exchanger during start-up of transcritical refrigeration system is investigated in this article. The work is focused on the local transient analysis of CO2thermophysical properties, in order to see how these transient changes affect the heat transfer rate and the effectiveness of internal heat exchanger, as well as the coefficient of performance during the start-up of the system. The study is conducted through a numerical simulation using the commercial computational fluid dynamics (CFD) software Ansys Fluent. Validation of numerical results is carried out by using seven different empirical correlations applied for the Nusselt number. It is observed that the thermophysical properties of the hot CO2stream experience large changes during the transient period. This instability is accompanied by a decrease in the heat transfer rate. Finally, the change in the internal heat exchanger effectiveness during the start-up results in a loss of about 12% of the coefficient of performance. [ABSTRACT FROM AUTHOR]

This paper investigates the results of a Second Law analysis applied to a mobile air conditioning system (MACs) integrated with an internal heat exchanger (IHX) by considering R152a, R1234yf and R1234ze as low global warming potential (GWP) refrigerants and establishing R134a as baseline. System simulation is performed considering the maximum value of entropy generated in the IHX. The maximum entropy production occurs at an effectiveness of 66% for both R152a and R134a, whereas for the cases of R1234yf and R1234ze occurs at 55%. Sub-cooling and superheating effects are evaluated for each one of the cases. It is also found that the sub-cooling effect shows the greatest impact on the cycle efficiency. The results also show the influence of isentropic efficiency on relative exergy destruction, resulting that the most affected components are the compressor and the condenser for all of the refrigerants studied herein. It is also found that the most efficient operation of the system resulted to be when using the R1234ze refrigerant. [ABSTRACT FROM AUTHOR]

The nuclear envelope (NE) forms a barrier between the nucleus and the cytosol that preserves genomic integrity. The nuclear lamina and nuclear pore complexes (NPCs) are NE components that regulate nuclear events through interaction with other proteins and DNA. Defects in the nuclear lamina are associated with the development of laminopathies. As cells depleted of phosphoinositide 3-kinase beta (PI3Kβ) showed an aberrant nuclear morphology, we studied the contribution of PI3Kβ to maintenance of NE integrity. pik3cb depletion reduced the nuclear membrane tension, triggered formation of areas of lipid bilayer/ lamina discontinuity, and impaired NPC assembly. We show that one mechanism for PI3Kβ regulation of NE/NPC integrity is its association with RCC1 (regulator of chromosome condensation 1), the activator of nuclear Ran GTPase. PI3Kβ controls RCC1 binding to chromatin and, in turn, Ran activation. These findings suggest that PI3Kβ regulates the nuclear envelope through upstream regulation of RCC1 and Ran. [ABSTRACT FROM AUTHOR]

The phosphoinositide 3-kinase (PI3K)/PTEN (phosphatase and tensin homolog) pathway is one of the central routes that enhances cell survival, division, and migration, and it is frequently deregulated in cancer. PI3K catalyzes formation of phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] after cell activation; PTEN subsequently reduces these lipids to basal levels. Activation of the ubiquitous p110β isoform precedes that of p110β at several points during the cell cycle. We studied the potential connections between p110β and p110β activation, and we show that cell stimulation promotes p110β and p110β association, demonstrating oligomerization of PI3K catalytic subunits within cells. Cell stimulation also promoted PTEN incorporation into this complex, which was necessary for PTEN activation. Our results show that PI3Ks dimerize in vivo and that PI3K and PTEN activities modulate each other in a complex that controls cell PI(3,4,5)P3 levels. [ABSTRACT FROM AUTHOR]

The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex. [ABSTRACT FROM AUTHOR]

Here we studied and characterized different peripheral blood (PB) regulatory T cell (Treg) subsets in rheumatoid arthritis (RA) patients and tested the hypothesis that changes in these cells can be linked to the degree of inflammation and relapsing/remission periods. PB cells were examined from RA subjects ( n = 60) with different disease activity score-28 (DAS28) and from healthy controls ( n = 40). Frequencies of Treg subsets expressing characteristic membrane antigens, FoxP3 or intracellular cytokines were quantified by flow cytometry. We observed a decrease in the percentages of CD4+CD25high, CD4+CD25int, CD4+CD25int/highFoxP3+, CD4+CD38+, CD4+CD62L+, CD8+CD25highCD45RA+ and CD8+CD25intCD45RA+ T cells in PB of RA patients compared to healthy controls. In addition, we found increased percentages of cells expressing membrane/intracellular regulatory antigens such as OX40 (CD134), CD45RBlow or CTLA-4 (CD152), and a higher proportion of other T cell subsets including CD4+CTLA-4+, CD4+IL10+, CD4+CD25intIL10+, CD4+CD25int TGFβ+, CD4+CD25low TGFβ+ and CD8+CD28− . We show that most of these changes parallel the intensity of inflammation, with lowest or highest values in patients with moderately/very active disease compared to healthy controls and at times to patients with inactive RA. The balance between these cell subsets and their antigen expression would determine the inflammation levels and could thus be linked to the relapsing/remission periods of the disease. [ABSTRACT FROM AUTHOR]

This work presents the main behaviors shown in the habits of consumers of domestic refrigerators, which influences the energy consumption of this appliance. This study is based on a series of surveys answered by 200 consumers from four cities in the State of Guanajuato, Mexico. The questions were arranged with the aim of evaluating the general characteristics and usage habits such as refrigerator age, door opening frequency, damper position, load of food supplies, external and internal cleaning habits, and nearby heat sources, among other things. The randomly interviewed consumers were individuals between 20 and 60 years of age, who were interviewed using handmade surveys by experts in the field of refrigeration. In some cases, photographic evidence was gathered from the consumers' refrigerators to represent the typical usage habits. In general, the results show that better usage habits are necessary from an energy point of view. Most consumers agree with adopting best practices for using their refrigerator. [ABSTRACT FROM AUTHOR]