The complete mitochondrial genome of Taeniogonalos taihorina (Bischoff) (Hymenoptera: Trigonalyidae) reveals a novel gene rearrangement pattern in the Hymenoptera

The family Trigonalyidae is considered to be one of the most basal lineages in the suborder Apocrita of Hymenoptera. Here, we determine the first complete mitochondrial genome of the Trigonalyidae, from the species Taeniogonalos taihorina (Bischoff, 1914). This mitochondrial genome is 15,927 bp long, with a high A + T-content of 84.60%. It contains all of the 37 typical animal mitochondrial genes and an A + T-rich region. The orders and directions of all genes are different from those of previously reported hymenopteran mitochondrial genomes. Eight tRNA genes, three protein-coding genes and the A + T-rich region were rearranged, with the dominant gene rearrangement events being translocation and local inversion. The arrangements of three tRNA clusters, trnY–trnM–trnI–trnQ, trnW–trnL2–trnC, and trnH–trnA–trnR–trnN–trnS–trnE–trnF, and the position of the cox1 gene, are novel to the Hymenoptera, even the insects. Six long intergenic spacers are present in the genome. The secondary structures of the RNA genes are normal, except for trnS2, in which the D-stem pairing is absent.     

Computational and experimental investigation of local stress fiber orientation in uniaxially and biaxially constrained microtissues

The orientation of cells and associated F-actin stress fibers is essential for proper tissue functioning. We have previously developed a computational model that qualitatively describes stress fiber orientation in response to a range of mechanical stimuli. In this paper, the aim is to quantitatively validate the model in a static, heterogeneous environment. The stress fiber orientation in uniaxially and biaxially constrained microscale tissues was investigated using a recently developed experimental system. Computed and experimental stress fiber orientations were compared, while accounting for changes in orientation with location in the tissue. This allowed for validation of the model, and additionally, it showed how sensitive the stress fiber orientation in the experimental system is to the location where it is measured, i.e., the heterogeneity of the stress fiber orientation. Computed and experimental stress fiber orientations showed good quantitative agreement in most regions. A strong local alignment near the locations where boundary conditions were enforced was observed for both uniaxially and biaxially constrained tissues. Excepting these regions, in biaxially constrained tissues, no preferred orientation was found and the distribution was independent of location. The stress fiber orientation in uniaxially constrained tissues was more heterogeneous, and stress fibers mainly oriented in the constrained direction or along the free edge. These results indicate that the stress fiber orientation in these constrained microtissues is mainly determined by the local mechanical environment, as hypothesized in our model, and also that the model is a valid tool to predict stress fiber orientation in heterogeneously loaded tissues.     

Computational model predicts cell orientation in response to a range of mechanical stimuli

To build anisotropic, mechanically functioning tissue, it is essential to understand how cells orient in response to mechanical stimuli. Therefore, a computational model was developed which predicts cell orientation, based on the actin stress fiber distribution inside the cell. In the model, the stress fiber distribution evolves dynamically according to the following: (1) Stress fibers contain polymerized actin. The total amount of depolymerized plus polymerized actin is constant. (2) Stress fibers apply tension to their environment. This active tension is maximal when strain rate and absolute strain are zero and reduces with increasing shortening rate and absolute strain. (3) A high active fiber stress in a direction leads to a large amount of fibers in this direction. (4) The cell is attached to a substrate; all fiber stresses are homogenized into a total cell stress, which is in equilibrium with substrate stress. This model predicts that on a substrate of anisotropic stiffness, fibers align in the stiffest direction. Under cyclic strain when the cellular environment is so stiff that no compaction occurs (1 MPa), the model predicts strain avoidance, which is more pronounced with increasing strain frequency or amplitude. Under cyclic strain when the cellular environment is so soft that cells can compact it (10 kPa), the model predicts a preference for the cyclically strained compared to the compacting direction. These model predictions all agree with experimental evidence. For the first time, a computational model predicts cell orientation in response to this range of mechanical stimuli using a single set of parameters.     

Divided we stand: splitting synthetic cells for their proliferation

With the recent dawn of synthetic biology, the old idea of man-made artificial life has gained renewed interest. In the context of a bottom-up approach, this entails the de novo construction of synthetic cells that can autonomously sustain themselves and proliferate. Reproduction of a synthetic cell involves the synthesis of its inner content, replication of its information module, and growth and division of its shell. Theoretical and experimental analysis of natural cells shows that, whereas the core synthesis machinery of the information module is highly conserved, a wide range of solutions have been realized in order to accomplish division. It is therefore to be expected that there are multiple ways to engineer division of synthetic cells. Here we survey the field and review potential routes that can be explored to accomplish the division of bottom-up designed synthetic cells. We cover a range of complexities from simple abiotic mechanisms involving splitting of lipid-membrane-encapsulated vesicles due to physical or chemical principles, to potential division mechanisms of synthetic cells that are based on prokaryotic division machineries.     

Skewed Brownian Fluctuations in Single-Molecule Magnetic Tweezers

Measurements in magnetic tweezers rely upon precise determination of the position of a magnetic microsphere. Fluctuations in the position due to Brownian motion allows calculation of the applied force, enabling deduction of the force-extension response function for a single DNA molecule that is attached to the microsphere. The standard approach relies upon using the mean of position fluctuations, which is valid when the microsphere axial position fluctuations obey a normal distribution. However, here we demonstrate that nearby surfaces and the non-linear elasticity of DNA can skew the distribution. Through experiment and simulations, we show that such a skewing leads to inaccurate position measurements which significantly affect the extracted DNA extension and mechanical properties, leading to up to two-fold errors in measured DNA persistence length. We develop a simple, robust and easily implemented method to correct for such mismeasurements.     

Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

Introduction  

Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).     

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

Introduction  

Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.     

Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus

Introduction  

There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134.