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CD4+ T cells play an essential role in chronic MC903-induced skin inflammation
No full textMC903 skin inflammation model is one of well-characterized murine models of atopic dermatitis and driven by TSLP-mediated type 2 inflammation. Since it can be prepared simply by repetitive applications of MC903 and shows consistent clinical results, this model has been widely used. However, in contrast to human atopic dermatitis which is chronic and closely related to TH2 cells, MC903 induces inflammations temporarily and even in the absence of T cells. Here, we modified the MC903 treatment schedule and developed a chronic MC903-induced skin inflammation model. Mice were sensitized with a high dose of MC903 and challenged with a low dose of MC903. Prior to challenge, mice were allowed to recover completely from the inflammation which occurred during the sensitization. The challenge of MC903 induced skin swelling and type 2 inflammations more rapidly, which was dependent on CD4+ T cells and IL-33. We expect that our mouse model will be beneficial for studying the late course of atopic dermatitis.MC903 skin inflammation model is one of well-characterized murine models of atopic dermatitis and driven by TSLP-mediated type 2 inflammation. Since it can be prepared simply by repetitive applications of MC903 and shows consistent clinical results, this model has been widely used. However, in contrast to human atopic dermatitis which is chronic and closely related to TH2 cells, MC903 induces inflammations temporarily and even in the absence of T cells. Here, we modified the MC903 treatment schedule and developed a chronic MC903-induced skin inflammation model. Mice were sensitized with a high dose of MC903 and challenged with a low dose of MC903. Prior to challenge, mice were allowed to recover completely from the inflammation which occurred during the sensitization. The challenge of MC903 induced skin swelling and type 2 inflammations more rapidly, which was dependent on CD4+ T cells and IL-33. We expect that our mouse model will be beneficial for studying the late course of atopic dermatitis.
Keywords: Atopic dermatitis; CD4(+) T cell; Challenge; IL-33; MC903; Sensitization.
Copyright © 2022 Elsevier Inc. All rights reserved.National Research Foundation of Kore
Total In Vitro Biosynthesis of the Thioamitide Thioholgamide and Investigation of the Pathway.
No full textThioholgamides are ribosomally synthesized and posttranslationally modified peptides (RiPPs), with potent activity against cancerous cell lines and an unprecedented structure. Despite being one of the most structurally and chemically complex RiPPs, very few biosynthetic steps have been elucidated. Here, we report the complete in vitro reconstitution of the biosynthetic pathway. We demonstrate that thioamidation is the first step and acts as a gatekeeper for downstream processing. Thr dehydration follows thioamidation, and our studies reveal that both these modifications require the formation of protein complexes─ThoH/I and ThoC/D. Harnessing the power of AlphaFold, we deduce that ThoD acts as a lyase and also proposes putative catalytic residues. ThoF catalyzes the oxidative decarboxylation of the terminal Cys, and the subsequent macrocyclization is facilitated by ThoE. This is followed by Ser dehydration, which is also carried out by ThoC/D. ThoG is responsible for histidine bis-N-methylation, which is a prerequisite for His β-hydroxylation─a modification carried out by ThoJ. The last step of the pathway is the removal of the leader peptide by ThoK to afford mature thioholgamide. © 2022 American Chemical Society. All rights reserved.Thioholgamides are ribosomally synthesized and posttranslationally modified peptides (RiPPs), with potent activity against cancerous cell lines and an unprecedented structure. Despite being one of the most structurally and chemically complex RiPPs, very few biosynthetic steps have been elucidated. Here, we report the complete in vitro reconstitution of the biosynthetic pathway. We demonstrate that thioamidation is the first step and acts as a gatekeeper for downstream processing. Thr dehydration follows thioamidation, and our studies reveal that both these modifications require the formation of protein complexes─ThoH/I and ThoC/D. Harnessing the power of AlphaFold, we deduce that ThoD acts as a lyase and also proposes putative catalytic residues. ThoF catalyzes the oxidative decarboxylation of the terminal Cys, and the subsequent macrocyclization is facilitated by ThoE. This is followed by Ser dehydration, which is also carried out by ThoC/D. ThoG is responsible for histidine bis-N-methylation, which is a prerequisite for His β-hydroxylation─a modification carried out by ThoJ. The last step of the pathway is the removal of the leader peptide by ThoK to afford mature thioholgamide.Deutsche Forschungsgemeinschaft (DFG): MU 1254/32-1
J.K. thanks the BBSRC for support (BB/V016059/1). R.M. would like to acknowledge DFG (Leibniz Award: MU 1254/32-1)
IDENTIFICATION OF FERMENTATIONS BY POLYNOMIAL METHODS
No full textThe measure of the state variables of a fermentation
(biomass and substrate concentration) is always liable
to error. It is possible to reconstitute well enough
the rates of their variations during a transient state,
by a polynomial smoothing. By calculation of the derivative
polynomial, the values of the growth rate HM and
the global conversion rate R. at each moment can be deduced.
The fermentation parameters are then identified
through 2 linear smoothings.
The method is tested with data obtained by simulation
and given purposely noisy (known parameters). It is
applied in order to determine the growth parameters
of a continuous fermentation.
The advantage of this direct method upon the usual
sequential techniques is its rapidity and its small
occupation of the central memory of the computer.
It can be applied to continuous or discontinuous fermentation
STOFFWECHSELPHYSIOLOGISCHE UNTERSUCHUNGEN AN NUCLEINSÄURENKOMPONENTEN IM SCP (METHYLOMONAS CLARA)
No full textInvestigations on the metabolism of nucleic acid components in SCP
(Methylomonas clara)
If SCP is used as a protein source for animals and man, the nucleic
acids in the material deserve particular attention in view of purine
degradation. Man, domestic mammals, fowl and fish differ in the final
steps and possibly in the capacity of dietary purine metabolism. As a
model animal the dalmatian dog has proved suitable because of similarities
to man in digestive physiology as well as in the excretion of
purine metabolites largely as uric acid. If diets with 5 - 390g SCP/kg
were fed, only about 60 % of the purines consumed were excreted in
urine. Metabolic kinetics with (2- Lis urate under steady state conditions
indicated that only a few percent of urate flux were diverted into
the GI-tract. Thus the digestibility of nucleic acids appears to limit
the metabolic availability of purines. Furthermore, the form of nucleic
acids in SCP-diets was shown to influence plasma urate levels and renal
urate excretion to a considerable extent
Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.
No full textAcute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants
Calycomorphotria hydatis gen. nov., sp. nov., a novel species in the family Planctomycetaceae with conspicuous subcellular structures.
No full textA novel strain belonging to the family Planctomycetaceae, designated V22T, was isolated from sediment of a seawater fish tank in Braunschweig, Germany. The isolate forms pink colonies on solid medium and displays common characteristics of planctomycetal strains, such as division by budding, formation of rosettes, a condensed nucleoid and presence of crateriform structures and fimbriae. Unusual invaginations of the cytoplasmic membrane and filamentous putative cytoskeletal elements were observed in thin sections analysed by transmission electron microscopy. Strain V22T is an aerobic heterotroph showing optimal growth at 30 °C and pH 8.5. During laboratory cultivations, strain V22T reached generation times of 10 h (maximal growth rate of 0.069 h-1). Its genome has a size of 5.2 Mb and a G + C content of 54.9%. Phylogenetically, the strain represents a novel genus and species in the family Planctomycetaceae, order Planctomycetales, class Planctomycetia. We propose the name Calycomorphotria hydatis gen. nov., sp. nov. for the novel taxon, represented by the type strain V22T (DSM 29767T = LMG 29080T)
Stereoselective Synthesis of a Protected Side Chain of Meliponamycin A.
No full textThe Matteson homologation was found to be a versatile tool for the construction of the linear polyketide side chain of meliponamycin and related compounds in only four steps. The ester dienolate version of this reaction allowed the introduction of the unsaturated ester moiety in a highly stereoselective fashion. Boronate oxidation/deoxygenation and Sharpless dihydroxylation are additional key steps in the stereoselective construction of this highly functionalized tetrahydropyran ring system, which is characteristic of this substance classThe Matteson homologation was found to be a versatile tool for the construction of the linear polyketide side chain of meliponamycin and related compounds in only four steps. The ester dienolate version of this reaction allowed the introduction of the unsaturated ester moiety in a highly stereoselective fashion. Boronate oxidation/deoxygenation and Sharpless dihydroxylation are additional key steps in the stereoselective construction of this highly functionalized tetrahydropyran ring system, which is characteristic of this substance classFinancial support from Saarland University and the DFG (grants: Ka 880/13-1; Bruker Neo 500-447298507) is gratefully acknowledged.
We thank Christine Walt from Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) for support with the mass pectrometr
Alienimonas californiensis gen. nov. sp. nov., a novel Planctomycete isolated from the kelp forest in Monterey Bay.
No full textPlanctomycetes are environmentally and biotechnologically important bacteria and are often found in association with nutrient-rich (marine) surfaces. To allow a more comprehensive understanding of planctomycetal lifestyle and physiology we aimed at expanding the collection of axenic cultures with new isolates. Here, we describe the isolation and genomic and physiological characterisation of strain CA12T obtained from giant bladder kelp (Macrocystis pyrifera) in Monterey Bay, California, USA. 16S rRNA gene sequence and whole genome-based phylogenetic analysis showed that strain CA12T clusters within the family Planctomycetaceae and that it has a high 16S rRNA sequence similarity (82.3%) to Planctomicrobium piriforme DSM 26348T. The genome of strain CA12T has a length of 5,475,215 bp and a G+C content of 70.1%. The highest growth rates were observed at 27 °C and pH 7.5. Using different microscopic methods, we could show that CA12T is able to divide by consecutive polar budding, without completing a characteristic planctomycetal lifestyle switch. Based on our data, we suggest that the isolated strain represents a novel species within a novel genus. We thus propose the name Alienimonas gen. nov. with Alienimonas californiensis sp. nov. as type species of the novel genus and CA12T as type strain of the novel species
OPTIMIZATION OF FERMENTATION PLANTS
No full textTechniques for estimation of investment and manufacturing costs in fermentation
are discussed.
A method for optimization of fermentation Plants as whole is described. 5
It necessitates knowledge of a model of the biosynthesis and equations correlating
investment and manufacturing costs to the size of equipment.
The Minimization of the non-linear objective function in a non-convex field
is obtained by a two step method.
Optimization in fermentation industry may have numerous aspects. One may envision
improving the growth rate, the production rate or the yield in compound biosynthesis.
In this case, the main control parameters are : substrate concentrations,
temperature, pH, aeration and agitation etc... Since a mathematical model of microbial
cell-growth has been formulated by Monod (1), the kinetic pattern of various
fermentation systems has been intensively studied. The number of publications in
this field is strongly increasing (2,3,4,5,6).
The problem concerning the reduction of manufacturing costs such as those of
steam, energy of agitation and aeration, consumption of air, water and raw materials
belong to another category of optimization. Okabe and Aiba have recently presented
solutions to these problems (7,8,9,10,11).
The purpose of this paper concerns the approach of a global optimization of a
new plan supposing that the annual production of a fermentation product is given,
then the optimization consists in determining the size of the fermentor, power of
agitation and aeration system, size of heat exchangers, pumps, filters, centrifuges
etc... the required condition for temperature, pH, dissolved oxygen, substrate concentration
etc... so that the investment capital and annual expenditure for the production
be minimized.
Since the same control variables and equipment are used in most fermentation industries,
we consider that the method proposed, as regards yeast production, will also
apply to various other production
WACHSTUMSVERHALTEN VON METHYLOMONAS CLARA
No full textA bacterium was chosen for single cell protein production from methanol
because of its high protein content of over 80% anda potential yield
of 0.6 g cell mass per g methanol. The selected organism Methylomonas
clara is an obligate methylotroph; methanol is incorporated as formaldehyde
via the ribulose monophosphate cycle.
The maximum possible cell mass production in continuous culture in two
different reactor systems was studied, to describe the kinetics of
growth. The reactors compared were a normal stirred vessel with a Flarblade
turbine and a newly designed completely filled bioreactor with a
draft tube and propeller. The maximum achieved cell mass productivity
in continuous culture in both reactor systems was 11.7 g . Ata
methanol concentration in the inflow medium of 100 g I wash out of
the cells occured at half maximum growth rate. By-products inhibition
limited further enhancment of growth. The proof was given experimentally