Take care of your belongings today – securing accessibility to complex electronic business processes

Most of today’s business processes are based solely on digital data. Input, output, and intermediate results are pure digital objects. Keeping such data accessible and meaningful but even more importantly keeping the business processes functional is challenging. With regards to complex electronic business processes traditional archiving does not provide satisfactory results. Due to the fast technical life-cycle the time gap between archiving and re-enactment or reuse of a process poses risks and increases the uncertainty on achievable results. We propose a novel strategy bridging this specific time gap. For this we present a scalable and cost-effective infrastructure with associated workflows focusing on a process’ execution context. Most importantly the process’ developers are able to assess the preserved results in a timely manner, and thus, reduce the uncertainty on future re-enactment results.     

Effect of Betaine and Arginine on Interaction of αB-Crystallin with Glycogen Phosphorylase b

Protein–protein interactions (PPIs) play an important role in many biological processes in a living cell. Among them chaperone–client interactions are the most important. In this work PPIs of αB-crystallin and glycogen phosphorylase b (Phb) in the presence of betaine (Bet) and arginine (Arg) at 48 °C and ionic strength of 0.15 M were studied using methods of dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation. It was shown that Bet enhanced, while Arg reduced both the stability of αB-crystallin and its adsorption capacity (AC₀) to the target protein at the stage of aggregate growth. Thus, the anti-aggregation activity of αB-crystallin increased in the presence of Bet and decreased under the influence of Arg, which resulted in inhibition or acceleration of Phb aggregation, respectively. Our data show that chemical chaperones can influence the tertiary and quaternary structure of both the target protein and the protein chaperone. The presence of the substrate protein also affects the quaternary structure of αB-crystallin, causing its disassembly. This is inextricably linked to the anti-aggregation activity of αB-crystallin, which in turn affects its PPI with the target protein. Thus, our studies contribute to understanding the mechanism of interaction between chaperones and proteins.     

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

MTEP,a Selective mGluR5 Antagonist,Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy

Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.     

AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.     

CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.     

Nutrient balance of shifting cultivation by burning or mulching in the Eastern Amazon – evidence for subsoil nutrient accumulation

For over a hundred years shifting cultivation with slash-and-burn land preparation has been the predominant type of land use by smallholders in the Bragantina region of the Brazilian Eastern Amazon. This study contrasts the nutrient balance of slash-and-burn agriculture with a fire-free cultivation. Therefore, one half of a 3.5-year-old (28.7 t DM ha^–1) and a 7-year-old woody fallow vegetation (46.5 t DM ha^–1) was burnt and the other half mulched, leaving the biomass as a surface residue. Subsequently, a sequence of maize, beans and cassava was cropped for 1.5 year. Burning the 3.5- and 7-year-old fallow removed 97 and 94% of the C, 98 and 96% of the N, 90 and 63% of the P-stocks, and between 45 and 70% of the cations K, Mg and Ca of the aboveground biomass by volatilization or ash-particle transfer. These losses were avoided with the slash-and-mulch land preparation. Mulching did not increase the losses of nutrients by leaching, despite the high amount of rapidly decomposing surface mulch. Also the length of preceding fallow had no significant influence on leaching losses. At a depth of 3 m, leached nutrients were quantitatively negligible in both treatments. Comparing the nutrient fluxes at soil depths of 0.9 m, 1.8 m and 3 m, the amounts of all mobile nutrients, and also of chloride and sodium were markedly reduced during percolation and must have been retained. It is likely that nutrient retention in the subsoil layer is only temporary, emphasizing the need for a rapid re-establishment of the naturally deep-rooting secondary vegetation after abandonment of sites to enable uptake of these nutrients. The overall nutrient balance was highly negative for slash-and-burn. 291 and 403 kg N ha^–1, 21 and 18 kg P ha^–1, and 70 and 132 kg K ha^–1 were removed from the burnt plots with a preceding fallow of 3.5 and 7 years, respectively. A reduced fallow period (3.5 years), which is a common trend in the region, resulted in a higher mean annual rate of nutrient loss averaged over the duration of the cycle than a fallow period of 7 years. Eliminating the burning losses by mulching brought the agricultural system back to an equilibrated or even slightly positive nutrient balance, even after a reduced fallow period. Thus, slash-and-mulch is a viable alternative to maintain agricultural productivity and ecosystem functioning.     

Effect of iron chelates on oil–water interface,stabilized by milk proteins: The role of phosphate groups and pH. Prediction of iron transfer from aqueous phase toward fat globule surface by changes of interfacial properties

Iron incorporated into food systems induces oxidation and precipitation. The consequences are reduced bioavailability and a functional modification of other food components such as proteins. The iron-chelates such as ferrous bisglycinate represent a possibility to avoid side effects, since the iron is protected. The aim of this study is to investigate the effects of iron-chelates compounds on the properties of an oil/water interface stabilized by caseinate or β-lacotoglobulin, under environmental conditions at 20 °C. Analyses were performed using dynamic drop tensiometry during 5000 s. The aqueous bulk phase is an imidazole/acetate buffer (0.1 M), containing 0.4 × 10⁻⁶ M protein, and 0.2 × 10^-6 9 M iron-chelates compounds. The results indicate that, under neutral conditions, the addition of some irons salts (NaFe-EDTA or Fe-bisglycinate) do not change the structure of the interface stabilized by a protein containing no phosphate groups (β-lactoglobulin). In the case of caseinate, NaFe-EDTA addition increases the lowering rate of surface tension at pH 6.5. On the contrary, the lowering rate of surface tension with caseinate is inhibited by Fe-bisglycinate at pH 6.5. Such an effect is not observed with β-lactoglobulin. The low transfer of irons ions from the bulk to the interface stabilized by β-lactoglobulin is confirmed by zetameter and FTIR measurements. These results indicate an effective strategy to follow for controlling the physical and chemical stability of an emulsion stabilized with proteins.