Impact of Leptin on Periodontal Ligament Fibroblasts during Mechanical Strain

Orthodontic treatment to correct dental malocclusions leads to the formation of pressure zones in the periodontal ligament resulting in a sterile inflammatory reaction, which is mediated by periodontal ligament fibroblasts (PDLF). Leptin levels are elevated in obesity and chronic inflammatory responses. In view of the increasing number of orthodontic patients with these conditions, insights into effects on orthodontic treatment are of distinct clinical relevance. A possible influence of leptin on the expression profile of PDLF during simulated orthodontic mechanical strain, however, has not yet been investigated. In this study, PDLF were exposed to mechanical strain with or without different leptin concentrations. The gene and protein expression of proinflammatory and bone-remodelling factors were analysed with RT-qPCR, Western-blot and ELISA. The functional analysis of PDLF-induced osteoclastogenesis was analysed by TRAP (tartrate-resistant acid phosphatase) staining in coculture with human macrophages. Pressure-induced increase of proinflammatory factors was additionally elevated with leptin treatment. PDLF significantly increased RANKL (receptor activator of NF-kB ligand) expression after compression, while osteoprotegerin was downregulated. An additional leptin effect was demonstrated for RANKL as well as for subsequent osteoclastogenesis in coculture after TRAP staining. Our results suggest that increased leptin concentrations, as present in obese patients, may influence orthodontic tooth movement. In particular, the increased expression of proinflammatory factors and RANKL as well as increased osteoclastogenesis can be assumed to accelerate bone resorption and thus the velocity of orthodontic tooth movement in the orthodontic treatment of obese patients.     

Combining fuzzy querying of imprecise data and predictive microbiology using category-based reasoning for prediction of the possible microbial spoilage in foods: application to Listeria monocytogenes

Various predictive models of microbial behavior have been created and extensive data collection has been done by numerous private or public laboratories. However, significant differences between predicted and observed values in foods have been observed and need to be stressed, understood and explained as much as possible. In this paper, we present a software tool (currently at the level of a prototype) able: (i) to store in a database all relevant information expressed on one hand as qualitative or quantitative data and on the other hand as precise or imprecise data; (ii) to retrieve the more relevant information from the database using queries where criteria may be expressed as fuzzy values in order to enhance the flexibility of the search: (iii) to compute, in addition to the nearest data, an estimation of searched values using statistical models. The architecture of this software tool is structured as a category-based reasoning system. Example queries about Listeria monocytogenes (L. monocytogenes) illustrate the functionalities of this tool.     

Three‐Dimensionally Ordered Macroporous Polymeric Materials by Colloidal Crystal Templating for Reversible CO2 Capture

The design and preparation of porous materials with controlled structures and functionalities is crucial to a variety of absorption‐ or separation‐relevant applications, including CO₂ capture. Here, novel functional polymeric materials with three‐dimensionally ordered macroporous (3DOM) structures are prepared by using colloidal crystals as templates using relatively simple, rapid, and inexpensive approaches. These ordered structures are used for the reversible CO₂ capture from ambient air by humidity swing. Typically, the colloidal crystal template is synthesized from polymer latex particles of poly(methyl methacrylate) (PMMA) or polystyrene (PS). To maintain the functionality of the material, it is important to prevent the porous structure collapsing, which can occur by the hydrolysis of the ester bonds in conventional crosslinkers under basic conditions. This hydrolysis can be prevented by using a water‐soluble crosslinker containing two quaternary ammonium moieties, which can be used to prepare stable porous crosslinked polymers with the monomer (vinylbenzyl)trimethylammonium chloride (VBTMACl) and using a PMMA‐based colloidal crystal template. The hydroxide‐containing monomer and dicationic crosslinker are synthesized from their chloride precursors, avoiding the ion‐exchange step which causes shrinkage of the pores. An analysis of different methods for infiltrating the monomer solution into the colloidal crystal template shows that infiltration using capillary forces leads to fewer defects than infiltration under a partial vacuum. In addition, functional macroporous films with micrometer thickness are prepared from a template of PS‐based colloidal crystals in a thin film. In general, the colloidal crystal templated materials showed improved CO₂ absorption/desorption rates and swing sizes compared to a commercially available material with similar functional groups. This work could easily be extended to create a new generation of ordered macroporous polymeric materials with tunable functionalities for other applications.     

Fade and quench-resistant emission in calcium phosphate nanoreactors

The fluorescence emission and photodegradation properties of fluorescein dye inside fluid-filled spherical nanoreactors ～ 150 nm in diameter and surrounded by a few nanometres thick layer of calcium phosphate are considered in detail. Steady state, stopped flow, and laser pulsed fluorescence spectroscopies, absorption spectroscopy, dynamic light scattering and electron microscopy were used to characterize the materials as a function of encapsulated dye concentration, particle concentration, illumination time, and pH. Fluorescein tends to form stable J-aggregates inside the nanoreactors. The molecular collision rate constants between the dye aggregates and between the dyes and soluble quenchers are greatly reduced inside the nanoreactors and are responsible for the observed resistance to photodegradation and reduced emission quenching. A model for dye behaviour in nanoreactors is suggested. Nanoreactors can be concentrated to a high suspension concentration, yielding exceptionally strong luminescence affected only by inner filter effects absent particle-particle crosstalk. These and similar nanoreactors can be utilized as building blocks for three-dimensional photo-optical devices, and as versatile and resilient supramolecular chromophores or tracers in complex fluids, cells and microfluidic systems where high resolution visualization is needed.     

Acetyldiaminobutanoic acid,a potential lathyrogenic amino acid in leaves of Acacia angustissima

Acacia angustissima has potential in agroforestry systems for forage production in tropical environments. However, feeding trials indicate that the leaves are potentially toxic. Signs of toxicity in sheep are similar to those presented by sheep fed flatpea (Lathyrus sylvestris) hay which contains a high concentration of the non‐protein amino acid 2,4‐diaminobutanoic acid (DABA). Cation exchange chromatography, high‐performance liquid chromatography (HPLC) and NMR were used to isolate and identify the non‐protein amino acid in A angustissima leaves. A quantitative HPLC method was used to determine the content of the non‐protein amino acid in leaves from 20 accessions. The non‐protein amino acid was identified as 4‐N‐acetyl‐2,4‐diaminobutanoic acid (ADAB), previously reported to occur in seeds. The average and range in ADAB content were 16.8 and 10.6–25.4 mg g^?1 respectively. This content of ADAB is higher than the levels of DABA in flatpea hay that are toxic to sheep. © 2001 Society of Chemical Industry     

Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker

We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment.     

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.     

Maximal Pairs of Computably Enumerable Sets in the Computably Lipschitz Degrees

A set A is computably Lipschitz or cl-reducible, for short, to a set B if A is Turing reducible to B by an oracle Turing machine with use function ? such that ? is bounded by the identity function up to an additive constant, i.e., ?(n)??n+O(1). In this paper we study maximal pairs of computably enumerable (c.e.) cl-degrees or maximal pairs, for short, i.e., pairs of c.e. cl-degrees such that there is no c.e. cl-degree that is above both cl-degrees in this pair. Our main results are as follows. (1) A c.e. Turing degree contains a c.e. cl-degree that is half of a maximal pair if and only if this Turing degree contains a maximal pair if and only if this Turing degree is array noncomputable. (2) The cl-degrees of all weak truth-table complete sets are halves of maximal pairs while there is a Turing complete set A such that the cl-degree of A is not half of any maximal pair. In fact, any high c.e. Turing degree contains a c.e. cl-degree that is not half of a maximal pair. (3) Above any c.e. cl-degree there is a maximal pair. (4) There is a maximal pair which at the same time is a minimal pair. (5) There is a pair of c.e. cl-degrees that is not maximal and does not possess a least upper bound. Moreover, we make some observations on the structure of the c.e. cl-degrees in general. For instance, we give a very simple proof of the fact that there are no maximal c.e. cl-degrees.