Basalt-epoxy laminates are establishing gradually in engineering sectors due to increasing attention toward environmental matters. Some properties should be improved to extend their applications and ...the cold spray (CS) metallization provides a potential solution. Unfortunately, the fragile nature of thermosetting polymers makes it difficult the CS coating formation and grow-up. Therefore, this research work aims to study an innovative solution able to enhance the adhesion mechanisms between the cold sprayed metal particles and the thermosetting polymer-based substrates. For this purpose, an original manufacturing method that provides the surface PLA treatment for thermosetting samples was developed. AlSi10Mg particles were cold sprayed on the treated surface, and the low-velocity impact behaviour of the metallised hybrid structures was analysed in details. The outcomes prove the effectiveness of the method proposed on the deposition process and the beneficial effects of metallization on impact damage mechanisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rare mutations in
CIDEB
protect against liver disease, making the gene a candidate target for treatment. Suppression of CIDEB interferes with the formation of fat droplets in cells.
Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined ...whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27-40 weeks' gestation from women with early-onset PE (
= 20) and gestation-matched normotensive control pregnancies (
= 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (
) and guanidinoacetate methyltransferase (
), the creatine transporter (
), and the creatine kinases (mitochondrial
& cytosolic
) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (
< 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal ...maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research "road forward" to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.
Creatine metabolism likely contributes to energy homeostasis in the human uterus, but whether this organ synthesizes creatine and whether creatine metabolism is adjusted throughout the menstrual ...cycle and with pregnancy are largely unknown. This study determined endometrial protein expression of creatine-synthesizing enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), creatine kinase (CKBB), and the creatine transporter (SLC6A8) throughout the menstrual cycle in fertile and primary infertile women. It also characterized creatine metabolism at term pregnancy, measuring aspects of creatine metabolism in myometrial and decidual tissue. In endometrial samples, AGAT, GAMT, SLC6A8, and CKBB were expressed in glandular and luminal epithelial cells. Except for SLC6A8, the other proteins were also located in stromal cells. Irrespective of fertility, AGAT, GAMT, and SLC6A8 high-intensity immunohistochemical staining was greatest in the early secretory phase of the menstrual cycle. During the proliferative phase, staining for SLC6A8 protein was greater (P = 0.01) in the primary infertile compared with the fertile group. Both layers of the term pregnant uterus contained creatine, phosphocreatine, guanidinoacetic acid, arginine, glycine, and methionine; detectable gene and protein expression of AGAT, GAMT, CKBB, and ubiquitous mitochondrial CK (uMt-CK); and gene expression of SLC6A8. The proteins AGAT, GAMT, CKBB, and SLC6A8 were uniformly distributed in the myometrium and localized to the decidual glands. In conclusion, endometrial tissue has the capacity to produce creatine and its capacity is highest around the time of fertilization and implantation. Both layers of the term pregnant uterus also contained all the enzymatic machinery and substrates of creatine metabolism. Summary Sentence The human uterus has the capacity to produce, transport and metabolise creatine during the menstrual cycle and at term pregnancy, with this capacity is up-regulated during the early secretory phase of the menstrual cycle. Graphical Abstract
Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the ...United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (
,
,
,
, and
). Protein-truncating variants in
were observed in ~4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of
in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate ...and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. We identified associations between an Amish-enriched ...missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (
) and 13.9 milligrams per deciliter lower LDL-C (
= 4.1 × 10
) and 29 milligrams per deciliter lower plasma fibrinogen (
= 1.3 × 10
).
gene–based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64,
= 0.006). The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin.
Ser knock-in mice showed decreases in LDL-C and fibrinogen. Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease.
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