Interleukin-32δ interacts with IL-32β and inhibits IL-32β-mediated IL-10 production

There is growing evidence for multifunctional properties of IL-32. We previously demonstrated that IL-32β upregulates IL-10 production through the association with PKCδ. In this study, we examined the effects of other IL-32 isoforms on IL-10 production. We found that IL-32δ decreased IL-10 production and investigated the inhibitory mechanism of IL-32δ. We showed that IL-32δ suppressed IL-32β binding to PKCδ by interacting with IL-32β. The inhibitory effect of IL-32δ on IL-32β association with PKCδ was further verified by immuno-fluorescence staining. The co-localization of IL-32β and PKCδ around the nuclear membrane was disrupted by IL-32δ. Our data therefore indicate that IL-32δ plays an inhibitory role against IL-32β function, which also suggests that IL-32 may be regulated by its own isoform.     

Carbon isotope signatures reveal that diet is related to the relative sizes of the gills and palps in bivalves

In marine bivalves, the relative sizes of the gills and palps appear to be a useful functional trait that reflect feeding mode, i.e. suspension feeders have relatively larger gills than palps for pumping, whereas deposit feeders have relatively larger palps than gills for sorting. Also, within a species, the relative sizes of the gills and palps are related to changes in local food conditions. However, there is still no firm evidence showing that differences in the relative gill and palp sizes between species are related to diet selection. Based on the knowledge that carbon and nitrogen isotope signatures of an animals tissues reflect past diet, we compared the relative gill and palp sizes of bivalves from Roebuck Bay, northwestern Australia with their carbon and nitrogen isotope signatures. The carbon isotope signatures distinguished clear differences in diet between bivalves along a gradient from suspension to deposit feeding, and strikingly this pattern was closely followed by the relative sizes of the gills and palps of the bivalves. This study confirms that relative gill and palp sizes in bivalves are a functional trait that can be used to compare resource use between species. Furthermore, these data may suggest that morphospace occupation, as determined by relative gill and palp sizes of bivalves, could reflect a gradient of resource use between species.     

Vertical foodweb structure of freshwater zooplankton assemblages estimated by stable nitrogen isotopes

Although theoretical foodweb models predict the presence of only three to four trophic categories, estimation of “potential” vertical foodweb structure from species lists and inferred feeding interactions suggest that as many as 7 trophic categories can occur in the pelagic foodwebs of North American glaciated lakes. A compilation of data on the nitrogen isotopic composition of zooplankton from 46 Canadian Shield lakes suggested the average existence of one “realized” trophic category in addition to that of filter-feeding, herbivorous cladocerans. When phytoplankton, planktivorous invertebrates, and plantivorous and piscivorous fish are included, the vertical foodweb structure in the pelagic zones of these lakes are greater than those hypothesized from some theoretical models.     

Epitope mapping of an anti-diacylglycerol kinase delta monoclonal antibody DdMab-1

Diacylglycerol kinase δ (DGKδ) is a type II DGK, which catalyzes diacylglycerol phosphorylation to produce phosphatidic acid. DGKδ is expressed in several types of tissues and organs including the stomach, testis, bone marrow, and lymph node. Here, we established an anti-human DGKδ (hDGKδ) mAb, DdMab-1 (mouse IgG_2a, kappa), which is useful for Western blot analysis. We also introduced deletion or point mutations to hDGKδ, and performed western blotting to determine the binding epitope of DdMab-1. DdMab-1 reacted with the dN670 mutant, but not with the dN680 mutant, indicating that the N-terminus of the DdMab-1 epitope is mainly located between amino acids 670 and 680 of the protein. Further analysis using point mutants demonstrated that R675A, R678A, K679A, and K682A mutants were not detected, and V680A was only weakly detected by DdMab-1, indicating that Arg675, Arg678, Lys679, Val680 and Lys682 are important for binding of DdMab-1 to hDGKδ.     

Two new diterpenoids from the roots of Pygmacopremna herbacea

Two new diterpenoids, neobharangi-δ-lactone (1) and bharangi quinone (2) along with two known compounds neobharangin (3) and bharangin (4) were isolated from the ethyl acetate extract of root nodules of Pygmacopremna herbacea. The structures of the new compounds were established by 1D and 2D NMR spectroscopic data.     

N-(1H-Pyrazol-3-yl)quinazolin-4-amines as a novel class of casein kinase 1δ/ε inhibitors: Synthesis,biological evaluation and molecular modeling studies

Described herein is the design, synthesis and biological evaluation of a series of N-(1H-pyrazol-3-yl)quinazolin-4-amines against a panel of eight disease relevant protein kinases. The kinase inhibition results indicated that two compounds inhibited casein kinase 1δ/ε (CK1δ/ε) with some selectivity over related kinases, namely CDK5/p25, GSK-3α/β, and DYRK1A. Docking studies with 3c and 3d revealed the key interactions with desired amino acids in the ATP binding site of CK1δ. Furthermore, compound 3c also elicited selective cytotoxic activity against the pancreas ductal adenocarcinoma (PANC-1) cell line. Taken together, the results of this study establish N-(1H-pyrazol-3-yl)quinazolin-4-amines especially 3c and 3d as valuable lead molecules with great potential for CK1δ/ε inhibitor development targeting neurodegenerative disorders and cancer.     

A bimodular PKS platform that expands the biological design space

Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be engineered as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated the first module of the lipomycin PKS to produce short chain ketones, 3-hydroxy acids, and saturated, branched carboxylic acids. Building upon this work, we have expanded to multi-modular systems by engineering the first two modules of lipomycin to generate unnatural polyketides as potential biofuels and specialty chemicals in Streptomyces albus. First, we produce 20.6 mg/L of the ethyl ketone, 4,6 dimethylheptanone through a reductive loop exchange in LipPKS1 and a ketoreductase knockouts in LipPKS2. We then show that an AT swap in LipPKS1 and a reductive loop exchange in LipPKS2 can produce the potential fragrance 3-isopropyl-6-methyltetrahydropyranone. Highlighting the challenge of maintaining product fidelity, in both bimodular systems we observed side products from premature hydrolysis in the engineered first module and stalled dehydration in reductive loop exchanges. Collectively, our work expands the biological design space and moves the field closer to the production of “designer” biomolecules.     

Upper Katian (Upper Ordovician) trans-Atlantic δ13C chemostratigraphy: the geochronological equivalence of the ELKHORN and PAROVEJA excursions and its implications

Since 2010 when the North American ELKHORN and Baltoscandic PAROVEJA isotope excursions were first described and named, their mutual age relations have remained uncertain, if not controversial. This was at least partly due to the incompleteness of the ELKHORN excursion in its reference section in western Ohio. The unexpected discovery of an apparently complete ELKHORN excursion in a drill core from St Marys in western Ohio has led to the conclusion that in terms of stratigraphical position and δ¹³C curve correspondence, the ELKHORN and PAROVEJA excursions are so similar that they apparently represent the same isotopic curve perturbation. The ELKHORN/PAROVEJA excursion occurs in the D. pacificus Graptolite Zone and uppermost A. ordovicicus Conodont Zone in the uppermost Katian Stage (Stage Slice Ka4 of Bergström et al. Lethaia 42, 97–197, 2009). Because the designation PAROVEJA was published two months before that of ELKHORN, it has priority as excursion designation. This excursion is particularly well represented in the carbonate successions in the Great Basin of western United States. Chemostratigraphy and biostratigraphy in that region show that the Richmondian transgression was contemporaneous with the beginning of the middle Katian WHITEWATER/MOE excursion. The onset of the Richmondian transgression has long been controversial but now available evidence suggests that it is of essentially the same age across large regions of the southern, western and central United States.     

Δ5-Dehydroskytanthin und 8-skytanthin in Tecoma stans

The structures of two new alkaioids extracted from Tecoma stans were determined by IR, NMR, MS and m.ps of their picrates and methoiodides. The compounds were characterized as Δ⁵ -dehydroskytanthine and δ-skytanthine.     

Inhibition of steroid-mediated induction of δ-aminolevulinic acid synthase by 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A)

The inhibition of the steroid-mediated induction of δ-aminolevulinate synthase, the rate-limiting enzyme in hepatic porphyrin-heme biosynthesis, by 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) as studied in cultured chick embryo liver cells. The formation of porphyrins in response to cyproterone, a synthetic steroid, was inhibited in a time-dependent manner by SKF 525-A, an inhibitor of several drug metabolizing enzyme systems. This action is a result of an inhibitory effect of SKF 525-A on the cyproterone-mediated induction of δ-aminolevulinate synthase; SKF 525-A laso inhibited the induction of the enzyme by the naturally occurring 5β-H steroids, etiocholanolone and pregnanolone. Employing [³H]etiocholanolone, we provide evidence that this inhibition is not associated with either decreased uptake or an altered metabolism of the steroid. Moreover, approx. 4–6-fold more radioactivity was associated with [³H]etiocholanolone-treated cells cultured in the presence of SKF 525-A. Alternative mechanisms for the induction of δ-aminolevulinate synthase by steroids are proposed which do not require the interaction of steroid-receptor complex with the genome.