Controlling the Maillard reaction may affect the generation of 2-acetyl-1-pyrroline, the key aroma compound in rice. In this study, the kinetics of 2-acetyl-1-pyrroline accumulation in the glucose/proline model system was comprehensively investigated and extra methylglyoxal or glyoxal was added to enhance 2-acetyl-1-pyrroline concentrations during rice cooking. Using the multi-response kinetic modeling to derive kinetic parameters, the formation of glyoxal, as the reactive intermediate, was rate-determining for the overall generation rate of 2-acetyl-1-pyrroline. Besides, although 2-acetyl-1-pyrroline generation was easier to occur with lower activation energy, much higher depletion rates of 2-acetyl-1-pyrrroline at 120 °C and 140 °C led to maximal 2-acetyl-1-pyrroline accumulation at the lower temperature of 100 °C. Furthermore, the inclusion of 0.05 μmol/kg additional methylglyoxal in cooked rice significantly enhanced 2-acetyl-1-pyrroline generation. The work suggested that the development of rice products with superior flavor quality may be achieved by the slight accumulation of intermediates prior to thermal processing.

Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical \"one drug\"-\"one target\" paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.

Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules including nucleic acids, proteins, polysaccharides, and lipids. In addition to functioning within lysosomes, lysosomal enzymes are also secreted. Alterations in the levels and activities of lysosomal enzymes dysregulates lysosomes, which can lead to the intralysosomal accumulation of biological material and the development of lysosomal storage diseases (LSDs) in humans. Dictyostelium discoideum has a long history of being used to study the trafficking and functions of lysosomal enzymes. More recently, it has been used as a model system to study several LSDs. In this chapter, we outline the methods for assessing the activity of several lysosomal enzymes in D. discoideum (α-galactosidase, β-galactosidase, α-glucosidase, β-glucosidase, β-N-acetylglucosaminidase, α-mannosidase, cathepsin B, cathepsin D, cathepsin F, palmitoyl protein thioesterase 1, and tripeptidyl peptidase 1).

UNASSIGNED: 2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines.
UNASSIGNED: To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC-MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine.
UNASSIGNED: The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass-charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde.
UNASSIGNED: Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.

The human retina is a highly structured and complex neurosensory tissue central to perceiving and processing visual signals. In a healthy individual, the close interplay between the neuronal retina, the adjacent retinal pigment epithelium and the underlying blood supply, the choriocapillaris, is critical for maintaining eyesight over a lifetime. An impairment of this delicate and metabolically highly active system, caused by genetic alteration, environmental impact or both, results in a multitude of pathological phenotypes of the retina. Understanding and treating these disease processes are motivated by a marked medical need in young as well as in older patients. While naturally occurring or gene-manipulated animal models have been used successfully in ophthalmological research for many years, recent advances in induced pluripotent stem cell technology have opened up new avenues to generate patient-derived retinal model systems. Here, we explore to what extent these cellular models can be useful to mirror human pathologies in vitro ultimately allowing to analyze disease mechanisms and testing treatment options in the cell type of interest on an individual patient-specific genetic background.
Die menschliche Netzhaut ist ein hochstrukturiertes und komplexes neurosensorisches Gewebe, das eine zentrale Rolle in der Wahrnehmung und visuellen Verarbeitung optischer Signale spielt. Im gesunden Individuum ist das enge Zusammenspiel zwischen der neuronalen Netzhaut, dem eng benachbarten retinalen Pigmentepithel und der unmittelbaren Blutversorgung, der Choriokapillaris, kritisch für ein lebenslang intaktes Sehvermögen. Eine Beeinträchtigung dieses empfindlichen und metabolisch hochaktiven Systems, sei es durch genetische Veränderung, individuelle äußere Einflüsse oder beides, führt zu einer Vielfalt von pathologischen Phänotypen der Netzhaut. Verstehen und Behandeln dieser Krankheitsprozesse werden durch einen hohen medizinischen Bedarf an Therapieoptionen bei jungen, aber auch älteren Patienten, motiviert. Während natürlich vorkommende oder Gen-manipulierte Tiermodelle viele Jahre erfolgreich in der Gesundheitsforschung eingesetzt wurden, haben jüngere Entwicklungen im Bereich der induzierten pluripotenten Stammzell-Technologie neue, bisher nicht bekannte Möglichkeiten geschaffen, Patienten-abgeleitete Zellmodelle der Netzhaut zu generieren. In diesem Review möchten wir explorieren, in welchem Maße solche zellulären Modelle hilfreich sein können die menschlichen Pathologien in vitro abzubilden und somit deren Krankheitsmechanismen zu verstehen, was wiederum zu Behandlungsoptionen in einem definierten Zelltyp auf einem individuellen Patienten-spezifischen genetischen Hintergrund erlauben würde.

Epidermolysis bullosa acquisita (EBA) is a muco-cutaneous autoimmune disease characterized and caused by autoantibodies targeting type VII collagen (COL7). The treatment of EBA is notoriously difficult, with a median time to remission of 9 months. In preclinical EBA models, we previously discovered that depletion of regulatory T cells (Treg) enhances autoantibody-induced, neutrophil-mediated inflammation and blistering. Increased EBA severity in Treg-depleted mice was accompanied by an increased cutaneous expression of interferon gamma (IFN-γ). The functional relevance of IFN-γ in EBA pathogenesis had been unknown. Given that emapalumab, an anti-IFN-γ antibody, is approved for primary hemophagocytic lymphohistiocytosis patients, we sought to assess the therapeutic potential of IFN-γ inhibition in EBA. Specifically, we evaluated if IFN-γ inhibition has modulatory effects on skin inflammation in a pre-clinical EBA model, based on the transfer of COL7 antibodies into mice. Compared to isotype control antibody, anti-IFN-γ treatment significantly reduced clinical disease manifestation in experimental EBA. Clinical improvement was associated with a reduced dermal infiltrate, especially Ly6G+ neutrophils. On the molecular level, we noted few changes. Apart from reduced CXCL1 serum concentrations, which has been demonstrated to promote skin inflammation in EBA, the expression of cytokines was unaltered in the serum and skin following IFN-γ blockade. This validates IFN-γ as a potential therapeutic target in EBA, and possibly other diseases with a similar pathogenesis, such as bullous pemphigoid and mucous membrane pemphigoid.

The dentition of the chelal moveable digit in cohabiting astigmatids from UK beehives (i.e., Carpoglyphus lactis (Linnaeus), Glycyphagus domesticus (DeGeer), and Tyrophagus putrescentiae (Schrank)) is characterised for the first time using quantitative tribological measures within a 2D mechanical model. The trophic function of astigmatid chelae are reviewed in terms of macroscopic tools used by humans including hooking devices, pliers, shears, rasps and saws. Comparisons to oribatid claws and isopod dactyli are made. The overall pattern of the moveable digit form of T. putrescentiae is not just a uniformly shrunken/swollen version between the other two taxa at either the macro- or micro-scale. Mastication surface macro-roughness values are in the range of international Roughness Grade Numbers N5-N6. The moveable digit of C. lactis has low rugosity values compared to the glycyphagid and acarid (which are topographically more similar and match that roughness typical of some coral reef surfaces). C. lactis has the most plesiomorphic moveable digit form. The mastication surface of all three species as a chewing tool is distinctly ornamented despite the moveable digit of C. lactis looking like a bar-like beam. The latter has more opportunities to be a multifunctional tool behaviourally than the other two species. Little evidence of any differences in the \'spikiness\' of any \'toothiness\' is found. Some differences with laboratory cultured specimens are found in C. lactis and possibly T. putrescentiae suggesting where selection on the digit may be able to occur. The chelal surface of T. putrescentiae has been deformed morphologically during evolution the most, that of C. lactis the least. Repeated localised surface differentiation is a feature of the moveable digit in G. domesticus compared to the likely more concerted changes over certain nearby locations in T. putrescentiae. An impactful chelal teeth design is present in G. domesticus but this is more equivocal in T. putrescentiae. Pockets within the mastication surface of the glycyphagid (and to some extent for the acarid) may produce foodstuff crunch forces of the scale of the chelal tips of oribatids. The moveable digit dentition of G. domesticus is adapted to shred foodstuff (like a ripsaw) more than that of the grazing/shearing dentition of T. putrescentiae. The collecting \'picker\' design of C. lactis posterior teeth matches the size of Bettsia alvei hyphae which attacks hive-stored pollen. Detritus accumulated in chelal digit gullets through a sawing action matches the smallest observed ingested material. The dentition of C. lactis should produce less friction when moving through food material than G. domesticus. C. lactis is the most hypocarnivorous and may \'skim\' through fluids when feeding. Astigmatid teeth do matter. The three commensal species can avoid direct competition. Future work is proposed in detail.

Innate monocytes can be trained or reprogrammed to adopt distinct memory states, such as low-grade inflammation and immune exhaustion, bearing fundamental relevance to the pathogenesis of both acute diseases such as sepsis as well as chronic diseases such as atherosclerosis. Therefore, it is critically important to develop a regimen for generating memory monocytes in vitro in order to better define key monocyte memory states with diverse potentials for proliferation, differentiation, and activation, as well as underlying mechanisms. Here, we describe an efficient in vitro system to propagate a large number of highly purified murine memory monocytes through sustaining bone marrow-derived monocytes with macrophage colony-stimulating factor (M-CSF, 10 ng/mL)-containing medium, together with other polarization agents such as lipopolysaccharide (LPS) for a 5-day period. This method can yield high-purity monocytes, capable of exhibiting dynamic memory behaviors upon training with various polarizing agents.

This study investigated the potential use of fish paste from two pelagic species (Cetengraulis mysticetus or carduma in Colombia and Opisthonema sp. or plumuda in Colombia), either separately or combined, as a substitute for external fat sources in a Leberkäse product. Three stages were analyzed, evaluating biometric proportions, body performance, and meat batters containing different concentrations of fish pastes. Physicochemical and instrumental characterization analyses were performed to determine the effect of the type of fish paste and the level of its inclusion in the final product. Results showed that plumuda fish paste had higher protein and ash content than carduma fish paste, and the inclusion of carduma fish paste in meat batters led to a greater loss of liquid and lower emulsion and gel stability values. The study also established selection criteria for the two pelagic fish species that could be useful for the fishing industry. Overall, the study demonstrated that Leberkäse can be produced using these pelagic species with a relatively simple processing technology.

Research on mycorrhizal symbiosis has been slowed by a lack of established study systems. To address this challenge, we have been developing Suillus, a widespread ecologically and economically relevant fungal genus primarily associated with the plant family Pinaceae, into a model system for studying ectomycorrhizal (ECM) associations. Over the last decade, we have compiled extensive genomic resources, culture libraries, a phenotype database, and protocols for manipulating Suillus fungi with and without their tree partners. Our efforts have already resulted in a large number of publicly available genomes, transcriptomes, and respective annotations, as well as advances in our understanding of mycorrhizal partner specificity and host communication, fungal and plant nutrition, environmental adaptation, soil nutrient cycling, interspecific competition, and biological invasions. Here, we highlight the most significant recent findings enabled by Suillus, present a suite of protocols for working with the genus, and discuss how Suillus is emerging as an important model to elucidate the ecology and evolution of ECM interactions.