The Gestational Effects of Maternal Bone Marker Molecules on Fetal Growth,Metabolism and Long-Term Metabolic Health: A Systematic Review

Fetal exposure in adverse environmental factors during intrauterine life can lead to various biological adjustments, affecting not only in utero development of the conceptus, but also its later metabolic and endocrine wellbeing. During human gestation, maternal bone turnover increases, as reflected by molecules involved in bone metabolism, such as vitamin D, osteocalcin, sclerostin, sRANKL, and osteoprotegerin; however, recent studies support their emerging role in endocrine functions and glucose homeostasis regulation. Herein, we sought to systematically review current knowledge on the effects of aforementioned maternal bone biomarkers during pregnancy on fetal intrauterine growth and metabolism, neonatal anthropometric measures at birth, as well as on future endocrine and metabolic wellbeing of the offspring. A growing body of literature converges on the view that maternal bone turnover is likely implicated in fetal growth, and at least to some extent, in neonatal and childhood body composition and metabolic wellbeing. Maternal sclerostin and sRANKL are positively linked with fetal abdominal circumference and subcutaneous fat deposition, contributing to greater birthweights. Vitamin D deficiency correlates with lower birthweights, while research is still needed on intrauterine fetal metabolism, as well as on vitamin D dosing supplementation during pregnancy, to diminish the risks of low birthweight or SGA neonates in high-risk populations.     

Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms

Aging is one of the most intriguing processes of human ontogenesis. It is associated with the development of a wide variety of diseases affecting all organs and their systems. The victory over aging is the most desired goal of scientists; however, it is hardly achievable in the foreseeable future due to the complexity and ambiguity of the process itself. All body systems age, lose their performance, and structural disorders accumulate. The cardiovascular system is no exception. And it is cardiovascular diseases that occupy a leading position as a cause of death, especially among the elderly. The aging of the cardiovascular system is well described from a mechanical point of view. Moreover, it is known that at the cellular level, a huge number of mechanisms are involved in this process, from mitochondrial dysfunction to inflammation. It is on these mechanisms, as well as the potential for taking control of the aging of the cardiovascular system, that we focused on in this review.     

The mTOR Signaling Pathway in Multiple Sclerosis; from Animal Models to Human Data

This article recapitulates the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS). Key biological processes that intersect with mTOR signaling cascades include autophagy, inflammasome activation, innate (e.g., microglial) and adaptive (B and T cell) immune responses, and axonal and neuronal toxicity/degeneration. There is robust evidence that mTOR inhibitors, such as rapamycin, ameliorate the clinical course of the animal model of MS, experimental autoimmune encephalomyelitis (EAE). New, evolving data unravel mechanisms underlying the therapeutic effect on EAE, which include balance among T-effector and T-regulatory cells, and mTOR effects on myeloid cell function, polarization, and antigen presentation, with relevance to MS pathogenesis. Radiologic and preliminary clinical data from a phase 2 randomized, controlled trial of temsirolimus (a rapamycin analogue) in MS show moderate efficacy, with significant adverse effects. Large clinical trials of indirect mTOR inhibitors (metformin) in MS are lacking; however, a smaller prospective, non-randomized study shows some potentially promising radiological results in combination with ex vivo beneficial effects on immune cells that might warrant further investigation. Importantly, the study of mTOR pathway contributions to autoimmune inflammatory demyelination and multiple sclerosis illustrates the difficulties in the clinical application of animal model results. Nevertheless, it is not inconceivable that targeting metabolism in the future with cell-selective mTOR inhibitors (compared to the broad inhibitors tried to date) could be developed to improve efficacy and reduce side effects.     

Autotaxin Has a Negative Role in Systemic Inflammation

The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.     

UNICORE 6 — Recent and Future Advancements

UNICORE is a European Grid Technology with more than 10 years of history. Originating from the Supercomputing domain, the latest version UNICORE 6 has turned into a general-purpose Grid technology that follows established standards and offers a rich set of features to its users. The paper starts with an architectural insight into UNICORE 6, highlighting the workflow features, standards and the different clients. Next, the current state of advancement is presented by describing recent developments. The paper closes with an outlook on future planned developments.     

Effect of microwave heating on the migration of dioctyladipate and acetyltributylcitrate plasticizers from food-grade PVC and PVDC/PVC films into olive oil and water

Migration of dioctyladipate (DOA) and acetyltributylcitrate (ATBC) plasticizers from plasticized Polyvinylchloride (PVC) and polyvinylidene chloride (PVDC/PVC (Saran) films into both olive oil and distilled water during microwave heating has been studied. The plasticizer migrating into olive oil and water was determined using an indirect GC method after saponification of the ester-type plasticizer (DOA or ATBC) and subsequent collection of the alcohol component of the ester, namely: 2-ethyl-1-hexanol and 1-butanol, respectively. Migration was dependent on heating time, microwave power setting, the nature of the food simulant and the initial concentration of the plasticizer in the film. Migration of DOA into olive oil reached equilibrium after heating for 10 min at full power (604.6 mg DOA/1). Migration into distilled water was 74.1 mg/1 after 8 min of microwave cooking at full power. The amount of ATBC migrating into olive oil reached equilibrium after heating for 10 min at full power (73.9 mg ATBC/1). Migration into distilled water was 4.1 mg/1 after heating at full power for 8 min. Control samples containing olive oil gave DOA migration values which were significantly higher than the upper limit for global migration (60 mg/1) set by the European Community. It is proposed that PVC should not be used in direct contact with food in the microwave oven, while Saran may be used with caution in microwave heating and reheating applications, avoiding its direct contact with high fat foodstuffs.     

COVID-19 crisis impact on the stability between parties in crowdfunding and crowdsourcing

This research reviews challenges in building sustainable relationships between the parties involved in the crowdfunding and crowdsourcing projects, which are running in extreme situations, such as the COVID-19 pandemic. This study aims to solve problems that generate the crowdsourcing concerns and to find better alternatives to increase trust for crowdfunding among donors, as this impacts their strategic sustainability in the conditions of turbulence and COVID-induced financial crisis. It was found that factors influence donor decisions in different ways, yet the common tendency for donor activity is non-monotonicity. Future development in the field of sustainable relationships should focus on creating a donor classification system.

     

Enhancing Planar Inverted Perovskite Solar Cells with Innovative Dumbbell-Shaped HTMs: A Study of Hexabenzocoronene and Pyrene-BODIPY-Triarylamine Derivatives

Dumbbell-shaped systems based on PAHs-BODIPY-triarylamine hybrids TM-(01-04) are designed as novel and highly efficient hole-transporting materials for usage in planar inverted perovskite solar cells. BODIPY is employed as a bridge between the PAH units, and the effects of the conjugated π-system's covalent attachment and size are investigated. Fluorescence quenching, 3D fluorescence heat maps, and theoretical studies support energy transfer within the moieties. The systems are extremely resistant to UVC 254 nm germicidal light sources and present remarkable thermal stability at degradation temperatures exceeding 350 °C. Integrating these systems into perovskite solar cells results in outstanding power conversion efficiency (PCE), with TM-02-based devices exhibiting a PCE of 20.26%. The devices base on TM-01, TM-03, and TM-04 achieve PCE values of 16.98%, 17.58%, and 18.80%, respectively. The long-term stability of these devices is measured for 600 h, with initial efficiency retention between 94% and 86%. The TM-04-based device presents noticeable stability of 94%, better than the reference polymer PTAA with 91%. These findings highlight the exciting potential of dumbbell-shaped systems based on PAHs-BODIPY-triarylamine derivatives for next-generation photovoltaics.     

Children's Common Grounds: A Study of Intergroup Relations Among Children in Public Settings

This article discusses successful common grounds for children—public settings that enable the harmonious intermingling of children of different backgrounds, races, and ethnicities and that encourage their social interchange, play, educational development, and collaboration. Our study focused on three types of public space that tend to bring these children together: the public school, the park, and the neighborhood community center. The research employed a variety of methods to study the interaction of children 9 to 12 years of age. Field work took place at four sites in West Los Angeles, Santa Monica, and the San Fernando Valley that enjoy a high level of intermixing and have a reputation for promoting diversity. Subjects in the research included children, teachers, and administrators. The article highlights the findings of the field work and concludes with a comparative analysis of the different settings and a discussion of the environmental and programmatic attributes that contribute to their success.