The extended Elution by characteristic Point Method to determine Adsorption Isotherms of Labyrinthopeptin for Purification via Ion-Exchange Chromatography

Ion-exchange chromatography (IEC) is the most frequently used technique to purify proteins and therefore, plays an important role in process development for therapeutical proteins. To improve the purification using ion-exchange chromatography, adequate characterization of adsorption isotherms is obligatory. The Elution by Characteristic Point method (ECP) can be used to determine adsorption isotherms applying only minor amounts of sample material to the chromatography column. Here, the applicability of the extended ECP method to determine adsorption isotherms of the model protein bovine serum albumin (BSA) using bovine hemoglobin (bHb) as tracer substance to quantify all nonidealities of the system is shown. The resulting isotherm was validated using the static batch approach. In the next step, the gained knowledge is used to measure isotherms of Labyrinthopeptins A1 and A2, which show promising activity against retroviruses like herpes simplex virus or human immunodeficiency virus

Wire arc additive manufacturing (WAAM) of aluminium alloy AlMg5Mn with energy-reduced gas metal arc welding (GMAW)

Large-scale aluminum parts are used in aerospace and automotive industries, due to excellent strength, light weight, and the good corrosion resistance of the material. Additive manufacturing processes enable both cost and time savings in the context of component manufacturing. Thereby, wire arc additive manufacturing (WAAM) is particularly suitable for the production of large volume parts due to deposition rates in the range of kilograms per hour. Challenges during the manufacturing process of aluminum alloys, such as porosity or poor mechanical properties, can be overcome by using arc technologies with adaptable energy input. In this study, WAAM of AlMg5Mn alloy was systematically investigated by using the gas metal arc welding (GMAW) process. Herein, correlations between the energy input and the resulting temperature–time-regimes show the effect on resulting microstructure, weld seam irregularities and the mechanical properties of additively manufactured aluminum parts. Therefore, multilayer walls were built layer wise using the cold metal transfer (CMT) process including conventional CMT, CMT advanced and CMT pulse advanced arc modes. These processing strategies were analyzed by means of energy input, whereby the geometrical features of the layers could be controlled as well as the porosity to area portion to below 1% in the WAAM parts. Furthermore, the investigations show the that mechanical properties like tensile strength and material hardness can be adapted throughout the energy input per unit length significantl

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Evaluation of the Neurogenic Potential in the Rat Inferior Colliculus from Early Postnatal Days Until Adulthood

Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use