A Highly Focused Antigen Receptor Repertoire Characterizes γδ T Cells That are Poised to Make IL-17 Rapidly in Naive Animals

Interleukin (IL)-17 plays a key role in immunity. In acute infections, a rapid IL-17 response must be induced without prior antigen exposure, and γδ T cells are the major initial IL-17 producers. In fact, some γδ T cells make IL-17 within hours after an immune challenge. These cells appear to acquire the ability to respond to IL-1 and IL-23 and to make IL-17 naturally in naïve animals. They are known as the natural Tγδ17 (nTγδ17) cells. The rapidity of the nTγδ17 response, and the apparent lack of explicit T cell receptor (TCR) engagement for its induction have led to the view that this is a cytokine (IL-1, IL-23)-mediated response. However, pharmacological inhibition or genetic defects in TCR signaling drastically reduce the nTγδ17 response and/or their presence. To better understand antigen recognition in this rapid IL-17 response, we analyzed the antigen receptor repertoire of IL-1R+/IL-23R+ γδ T cells, a proxy for nTγδ17 cells in naïve animals, using a barcode-enabled high throughput single-cell TCR sequence analysis. We found that regardless of their anatomical origin, these cells have a highly focused TCR repertoire. In particular, the TCR sequences have limited V gene combinations, little or no junctional diversity and much reduced or no N region diversity. In contrast, IL-23R- cells at mucosal sites similar to most of the splenic γδ T cells and small intestine epithelial γδ lymphocytes expressed diverse TCRs. This remarkable commonality and restricted repertoire of IL-1R+/IL-23R+ γδ T cells underscores the importance of antigen recognition in their establishment/function

Strain alleviation in an isomorphous series of lanthanide 2-nitroterephthalates [Ln2(TPNO2)3(H2O)2]·2H2O (Ln = Pr – Lu, except Pm)

An extended series of trivalent lanthanide 2-nitroterephthalates, [Ln2(TPNO2)3(H2O)2]•2H2O, (Ln = Pr through Lu, except Pm) were synthesized hydrothermally from Ln2O3 and 2-nitroterephthalic acid (H2TPNO2) at 170˚C in Teflon lined Parr steel autoclaves, and were characterized via single crystal X-ray diffraction, powder X-ray diffraction, FT-IR spectroscopy, elemental analyses, and thermogravimetric analyses. All [Ln2(TPNO2)3(H2O)2]•2H2O coordination polymers are isomorphous, crystallizing in the monoclinic crystal system with space group C2/c. The metal centers in all networks possess the coordination number 8, while forming a three-dimensional extended lattice. Two metal centers form Ln2O14 entities, comprising crystallographically identical LnO8 polyhedra, connected via edge-sharing, utilizing two carboxylate O-atoms. These Ln2O14 units are separated along the a and b-axes by individual 2-nitroterephthalate linkers, while being closely connected along the c axis via two carboxylate groups on each side. Compared to small inorganic anions, the rather flexible 2-nitroterephthalate seems to allow for the unobstructed decrease in size of the LnO8 polyhedra as Ln3+ ionic radii decrease towards the heavier Ln elements. Hence, the structural parameters of the crystal lattice adjust gradually without noticeable strain buildup along the series resulting in isomorphous arrangements for all networks. The thermogravimetric and FT-IR measurements seem to confirm the structural features

Fermentation conditions that affect clavulanic acid production in Streptomyces clavuligerus: a systematic review

The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides an overview on the fermentation conditions that affect the production of clavulanic acid in the firstly described producer, Streptomyces clavuligerus. A thorough search was conducted using predefined terms in several electronic databases (PubMed, Medline, ScienceDirect, EBSCO), from database inception to June 30th 2015. Studies must involve wild-type Streptomyces clavuligerus, and full texts needed to be available. A total of 29 eligible articles were identified. Based on the literature, several factors were identified that could affect the production of clavulanic acid in S. clavuligerus. The addition of glycerol or other vegetable oils (e.g. olive oil, corn oil) could potentially affect clavulanic acid production. Furthermore, some amino acids such as arginine and ornithine, could serve as potential precursors to increase clavulanic acid yield. The comparison of different fermentation systems revealed that fed-batch fermentation yields higher amounts of clavulanic acid as compared to batch fermentation, probably due to the maintenance of substrates and constant monitoring of certain entities (such as pH, oxygen availability, etc.). Overall, these findings provide vital knowledge and insight that could assist media optimization and fermentation design for clavulanic acid production in S. clavuligerus

Strain Alleviation in an Isomorphous Series of Lanthanide 2-Nitroterephthalates [Ln2(TPNO2)3(H2O)2]·2H2O (Ln = Pr – Lu, except Pm)

An extended series of trivalent lanthanide 2-nitroterephthalates, [Ln2(TPNO2)3(H2O)2]·2H2O, (Ln = Pr through Lu, except Pm) were synthesized hydrothermally from Ln2O3 and 2-nitroterephthalic acid (H2TPNO2) at 170 °C in Teflon lined Parr steel autoclaves, and were characterized via single crystal X-ray diffraction, powder X-ray diffraction, FT-IR spectroscopy, elemental analyses, and thermogravimetric analyses. All [Ln2(TPNO2)3(H2O)2]·2H2O coordination polymers are isomorphous, crystallizing in the monoclinic crystal system with space group C2/c. The metal centers in all networks possess the coordination number 8, while forming a three-dimensional extended lattice. Two metal centers form Ln2O14 entities, comprising crystallographically identical LnO8 polyhedra, connected via edge-sharing, utilizing two carboxylate O-atoms. These Ln2O14 units are separated along the a- and b-axes by individual 2-nitroterephthalate linkers, while being closely connected along the c-axis via two carboxylate groups on each side. Compared to small inorganic anions, the rather flexible 2-nitroterephthalate seems to allow for the unobstructed decrease in size of the LnO8 polyhedra as Ln3+ ionic radii decrease towards the heavier Ln elements. Hence, the structural parameters of the crystal lattice adjust gradually without noticeable strain buildup along the series resulting in isomorphous arrangements for all networks. The thermogravimetric and FT-IR measurements seem to confirm the structural features

Concerted epithelial and stromal changes during progression of Barrett’s Esophagus to invasive adenocarcinoma exposed by multi-scale, multi-omics analysis

Esophageal adenocarcinoma arises from Barrett's esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue-mechanics and spatial proteomics of 64 samples from 12 patients' paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, revealed shared and patient-specific progression characteristics. The classic metaplastic replacement of epithelial cells was paralleled by metaplastic changes in stromal cells, ECM and tissue stiffness. Strikingly, this change in tissue state at metaplasia was already accompanied by appearance of fibroblasts with characteristics of carcinoma-associated fibroblasts and of an NK cell-associated immunosuppressive microenvironment. Thus, Barrett's esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporating stromal reprogramming