Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial

Introduction  

Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).     

Interaction between collagen and adenosine 5'-triphosphate.

A quantitative study was made of the adsorption of adenosine 5′-triphosphate (ATP) on collagen by following the change in the absorbance at 258 nm of ATP in the soaking solution. The amount of ATP adsorbed decreased exponentially with the increase of pH up to pH 8 and fell off more rapidly at higher pH values. At a given pH, when the concentration of ATP was increased, the amount of ATP adsorbed increased following the pattern of a Langmuir isotherm. The adsorption was independent of the cation present. The adsorption of adenosine 5′-diphosphate was essentially the same as that for ATP. For tendons deposited with calcium phosphate, the amount of ATP adsorbed decreased compared to natural tendons. The adsorption of ATP on collagen fibers inhibited the contraction caused by calcium chloride, calcium bromide, and lithium bromide. In solution, ATP had very little effect on the denaturation of acid-soluble collagen caused by calcium chloride.     

Investigation of Proposed Ladderane Biosynthetic Genes from Anammox Bacteria by Heterologous Expression in E. coli

Ladderanes are hydrocarbon chains with three or five linearly concatenated cyclobutane rings that are uniquely produced as membrane lipid components by anammox (anaerobic ammonia-oxidizing) bacteria. By virtue of their angle and torsional strain, ladderanes are unusually energetic compounds, and if produced biochemically by engineered microbes, could serve as renewable, high-energy-density jet fuel components. The biochemistry and genetics underlying the ladderane biosynthetic pathway are unknown, however, previous studies have identified a pool of 34 candidate genes from the anammox bacterium, Kuenenia stuttgartiensis, some or all of which may be involved with ladderane fatty acid biosynthesis. The goal of the present study was to establish a systematic means of testing the candidate genes from K. stuttgartiensis for involvement in ladderane biosynthesis through heterologous expression in E. coli under anaerobic conditions. This study describes an efficient means of assembly of synthesized, codon-optimized candidate ladderane biosynthesis genes in synthetic operons that allows for changes to regulatory element sequences, as well as modular assembly of multiple operons for simultaneous heterologous expression in E. coli (or potentially other microbial hosts). We also describe in vivo functional tests of putative anammox homologs of the phytoene desaturase CrtI, which plays an important role in the hypothesized ladderane pathway, and a method for soluble purification of one of these enzymes. This study is, to our knowledge, the first experimental effort focusing on the role of specific anammox genes in the production of ladderanes, and lays the foundation for future efforts toward determination of the ladderane biosynthetic pathway. Our substantial, but far from comprehensive, efforts at elucidating the ladderane biosynthetic pathway were not successful. We invite the scientific community to take advantage of the considerable synthetic biology resources and experimental results developed in this study to elucidate the biosynthetic pathway that produces unique and intriguing ladderane lipids.     

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints.     

Probing intra- versus interchain kinetic preferences of L-Thr acylation on dimeric VibF with mass spectrometry

We present a method to probe intra- and interchain activities within dimeric nonribosomal peptide synthetases. Utilizing domain inactivation and analytical mass mutants in conjunction with rapid-quench, mass spectrometry, and a probabilistic kinetic model, we have elucidated the pre-steady-state intra- and interchain rates and the corresponding flux of the acylation of L-Thr onto VibF. Although the intra rate is significantly faster than the inter rate, the data are most consistent with an even flux of covalent substrate loading where neither pathway dominates. These pre-steady-state results confirm previous steady-state in vitro mutant complementation studies of VibF. Extension of this methodology to other dimeric nonribosomal peptide synthetases, and to the related fatty acid and polyketide synthases, will further our biophysical understanding of their acyl-intermediate-processing pathways.     

Intrapopulation variation in macro tooth wear patterns—a case study from Igloolik,Canada

The pattern of human tooth wear—the way it varies between teeth in the mouth—is crucial to our understanding of important questions in archeology and paleoanthropology, such as the contrasts in diet and behavior between Neanderthals and early modern humans in Europe and Asia, or with the adoption of agriculture in the Americas. Little is known, however, about the way in which wear patterns develop with increasing age or the way in which they differ between males and females. One explanation is that few living people show the high rates of tooth wear seen worldwide throughout the preindustrial archaeological record. The study described here investigates the macroscopic pattern of tooth wear in a unique group of known age and sex dental casts from living Canadian Inuit from Igloolik. The results show that the Igloolik people possessed a pattern of extremely heavy anterior tooth wear, relative to the first molar and the other posterior teeth, which is attributed to the use of the anterior teeth in cultural practices as well as the extreme and marginal environments in which they lived. Heavy anterior tooth wear was established at an early age and maintained throughout life; statistically significant differences were found between the wear patterns of males and females and are explained in terms of sexual division of labor within the community. This study highlights the need to understand both intra‐ and interpopulation variation in tooth wear patterns when interpreting patterns in past human groups. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.     

DeviceEditor visual biological CAD canvas

Background  

Biological Computer Aided Design (bioCAD) assists the de novo design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.     

Technical note: A new three‐dimensional technique for high resolution quantitative recording of perikymata

The number and spacing of incremental markings at the enamel surface, known as perikymata, are considered important indicators of dental growth patterns, as they provide information on crown formation times and the underlying developmental processes. This study explores the potential of a new three‐dimensional technique for the reconstruction of dental growth profiles, using teeth from a medieval child from Abingdon, Oxfordshire. The crowns of three anterior teeth were imaged and analyzed using the Alicona 3D InfiniteFocus imaging microscope. Individual perikyma grooves can be unambiguously identified on a profile of the reconstructed enamel surface and direct distances between successive pairs of perikyma grooves can be calculated from coordinate data. This quantitative approach constitutes a more objective way to record perikymata spacing than current methods. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.     

Alternative dental measurements: proposals and relationships with other measurements

Most archaeological and fossil teeth are heavily worn, and this greatly limits the usefulness of tooth crown diameter measurements, as they are usually defined at the widest points of the crown. There are alternatives, particularly measurements at the cervix of the tooth, where the crown joints the root, and measurements along a diagonal axis in molars, that are much less affected by wear. These would allow a wider range of specimens to be included, e.g., in the study of dental reduction in Upper Palaeolithic and Mesolithic Homo sapiens. In addition, they would allow the little-worn teeth of children to be compared directly with well-worn teeth in adults. These alternatives, however, have been little used, and as yet there have not been any studies of the repeatability with which they can be measured, or of the extent to which they are related to the more usual crown diameters. The present study is based on a group of unworn teeth, where direct comparisons could be made between the alternative measurements, which are not much affected by wear, with the usual crown diameters, which are very much affected. In an interobserver-error study of this material, cervical and diagonal measurements could be recorded as reliably as the usual crown diameters. The buccolingual cervical measurement was strongly correlated with the normal bucclingual crown diameter in all teeth, whereas the mesiodistal cervical measurement was highly correlated with the normal mesiodistal crown diameter in incisors and canines, but less so in premolars and molars. The molar diagonal measurements showed high correlations with all other measurements. Crown areas (robustness index) calculated from the usual diameters were strongly correlated with crown areas calculated from cervical measurements, and crown areas calculated from molar diagonals were strongly correlated with both other areas. Despite the long usage of the more usual maximum crown diameters, the alternative dental measurements could be measured just as reliably, could record similar information about tooth crown size, and would be better measures for the worn dentitions seen in archaeological and fossil material.