Managing urban flood resilience through the English planning system: insights from the 'SuDS-face'.

In academic and professional circles, 'resilience thinking' has emerged as the dominant paradigm in flood risk management, which emphasizes the need to plan and design cities that can absorb water and replicate natural processes more closely. In this paper, we explore how planners in England are expected to respond to the resilience agenda against the realities in practice, zoning in on the delivery of sustainable (urban) drainage systems (SuDS). Our exploration highlights that, while SuDS are being implemented, they are largely characterized by a 'bog standard' design. We found that there are three main institutional factors that are constraining the implementation of SuDS: the lack of legislative backing, the power afforded to private commercial interests in the neoliberalized planning process, compounded by the severe lack of resources in local authorities. What is missing at the moment is SuDS process and design that is flexible, integrated, collaborative and innovative. There are clear implications that, without the necessary institutional support, resilience thinking will remain largely aspirational, and professionals will struggle to gain traction and translate the larger flood resilience policy agenda into England's future climate-resilient places. This article is part of the theme issue 'Urban flood resilience'.

Should endodontists place dental implants? A national survey of general dentists.

INTRODUCTION: The purpose of this study was to assess whether general dentists support the placement of dental implants by endodontists. METHODS: A 29-item written survey was developed and mailed to 1,500 randomly selected practicing general dentists within the United States to assess whether respondents supported implant placement by endodontists and whether they would refer patients to endodontists for implant placement. Univariate, bivariate, and logistic regression analyses were performed. RESULTS: Three hundred sixty-six subjects completed surveys. Sixty-six percent of respondents opposed endodontists placing implants, and 73% indicated they would not refer patients to an endodontist for implant placement. The following characteristics were associated with respondents who support implant placement (P < .05): yes, willing to refer to an endodontist for implant placement; believes other specialists would support endodontists placing implants; never or sometimes refers patients for molar root canal treatment; and plans to retire in 5 years. CONCLUSIONS: The majority of respondents did not support implant placement by endodontists. As the demand for implant therapy continues to grow, it may be necessary to increase the number of practitioners who place dental implants. However, general dentists' and specialists' attitudes should be further assessed before modifying the scope of endodontic practice to include implant placement.

Should endodontists place implants? A survey of U.S. endodontists.

INTRODUCTION: The purpose of this national study was to assess endodontists' opinions regarding whether endodontists should place dental implants. METHODS: A written survey was developed and mailed to 1505 randomly selected practicing endodontists within the United States. RESULTS: The response rate was 46%. Univariate, bivariate, and logistic regression analyses were performed. Fifty-seven percent of respondents supported endodontists placing implants. Currently 5.7% of respondents place implants. Regression analyses identified the following variables as being positively associated with endodontists placing implants: graduation from an endodontic training program >or=10 years ago (p = .002); interest in placing implants in the future (p = .0001); the belief that implant placement should be incorporated into the endodontic residency curriculum (p < .0001); the belief that general dentists would support endodontists placing implants (p < .0001); and the desire to continue the rapport with a referred patient by placing an implant if the patient's tooth is nonrestorable (p < .0001). CONCLUSIONS: The majority of responding endodontists believed that dental implant placement is within the scope of endodontic practice. Governing bodies of the specialty of endodontics might consider discussing whether formal implant training should be incorporated into future curricula.

Dental enamel: genes define biomechanics.

Regulated gene expression assembles an extracellular proteinaceous matrix to control biomineralization and the resultant biomechanical function of tooth enamel. The importance of the dominant enamel matrix protein, amelogenin (Amel); a minor transiently expressed protein, dentin sialoprotein (Dsp); an electrogenic sodium bicarbonate cotransporter (NBCe1); the timely removal of the proteinaceous matrix by a serine protease, Kallikrein-4 (Klk4); and the late-stage expression of Amelotin (Amtn) on enamel biomechanical function were demonstrated and measured using mouse models.

The inhibitory HVEM-BTLA pathway counter regulates lymphotoxin receptor signaling to achieve homeostasis of dendritic cells.

Proliferation of dendritic cells (DC) in the spleen is regulated by positive growth signals through the lymphotoxin (LT)-beta receptor; however, the countering inhibitory signals that achieve homeostatic control are unresolved. Mice deficient in LTalpha, LTbeta, LTbetaR, and the NFkappaB inducing kinase show a specific loss of CD8- DC subsets. In contrast, the CD8alpha- DC subsets were overpopulated in mice deficient in the herpesvirus entry mediator (HVEM) or B and T lymphocyte attenuator (BTLA). HVEM- and BTLA-deficient DC subsets displayed a specific growth advantage in repopulating the spleen in competitive replacement bone marrow chimeric mice. Expression of HVEM and BTLA were required in DC and in the surrounding microenvironment, although DC expression of LTbetaR was necessary to maintain homeostasis. Moreover, enforced activation of the LTbetaR with an agonist Ab drove expansion of CD8alpha- DC subsets, overriding regulation by the HVEM-BTLA pathway. These results indicate the HVEM-BTLA pathway provides an inhibitory checkpoint for DC homeostasis in lymphoid tissue. Together, the LTbetaR and HVEM-BTLA pathways form an integrated signaling network regulating DC homeostasis.

Endodontics and implants, a catalog of therapeutic contrasts.

Dentists may be faced with the choice to retain a tooth by performing endodontic therapy and restoration or to extract the tooth and replace it with an implant and restoration. The purpose of this study was to catalog areas where implant and endodontic therapies differ so as to assist dentists in making treatment decisions and in identifying areas deserving of future research. Differences in diagnostic procedures and prognostic indicators were listed. With respect to treatment outcomes, study designs, success criteria, treatment results, systematic reviews, complications, clinician expertise, and the use of patient-based measures were discussed. The need for clinically applicable consensus statements and treatment protocols was noted. It was concluded that at this time, choices between implant and endodontic therapies cannot be solely based on outcomes measurement evidence; that different modes of outcome measure frustrate direct comparison; that endodontic and implant therapies profoundly differ in many ways; that although rigorous and clearly defined outcome measures have been proposed for use in endodontic and implant outcomes studies, they are very rarely used; that long-term, large, clearly defined studies, with simple and clear outcome measures, for example survival in combination with defined treatment protocols, are needed to measure the clinical performance of endodontic and implant therapies; and it was recognized that broad outcomes data may not be sufficiently specific to directly impact clinical decision making.

Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway.

The herpesvirus entry mediator (HVEM), a member of the TNF receptor (TNFR) superfamily, can act as a molecular switch that modulates T cell activation by propagating positive signals from the TNF-related ligand LIGHT (TNFR superfamily 14), or inhibitory signals through the Ig superfamily member B and T lymphocyte attenuator (BTLA). Competitive binding analysis and mutagenesis reveals a unique BTLA binding site centered on a critical lysine residue in cysteine-rich domain 1 of HVEM. The BTLA binding site on HVEM overlaps with the binding site for the herpes simplex virus 1 envelope glycoprotein D, but is distinct from where LIGHT binds, yet glycoprotein D inhibits the binding of both ligands, potentially nullifying the pathway. The binding site on HVEM for BTLA is conserved in the orphan TNFR, UL144, present in human CMV. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation, selectively mimicking the inhibitory cosignaling function of HVEM. The demonstration that distinct herpesviruses target the HVEM-BTLA cosignaling pathway suggests the importance of this pathway in regulating T cell activation during host defenses.

Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor.

Mast cells are the major effector-cell type for immediate hypersensitivity and other forms of allergic reactions. Expression of 4-1BB, a member of the tumor necrosis factor receptor superfamily, is induced at mRNA and protein levels on stimulation through the high-affinity receptor for immunoglobulin E (IgE; FcepsilonRI). In this study, we present evidence that agonistic anti-4-1BB antibodies can enhance FcepsilonRI-induced cytokine production and secretion. Consistent with this, 4-1BB-deficient mast cells exhibit reduced degranulation and cytokine production on FcepsilonRI stimulation. Analysis of 4-1BB ligand (4-1BBL)-deficient cells supported this notion. As a potential mechanism for these defects, we identified a defect in Ca2+ flux induced by FcepsilonRI stimulation. The defective Ca2+ flux could be accounted for by the reduced activity of Lyn/Btk/phospholipase C-gamma2 pathway and constitutive interactions between 4-1BB and Lyn. Therefore, FcepsilonRI-inducible 4-1BB plays a costimulatory function together with FcepsilonRI stimulation.

B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator.

B and T lymphocyte attenuator (BTLA) provides an inhibitory signal to B and T cells. Previously, indirect observations suggested that B7x was a ligand for BTLA. Here we show that BTLA does not bind B7x; instead, we identify herpesvirus entry mediator (HVEM) as the unique BTLA ligand. BTLA bound the most membrane-distal cysteine-rich domain of HVEM, distinct from regions where the ligands LIGHT and lymphotoxin-alpha bound HVEM. HVEM induced BTLA tyrosine phosphorylation and association of the tyrosine phosphatase SHP-2 and repressed antigen-driven T cell proliferation, providing an example of reverse signaling to a non-tumor necrosis factor family ligand. The conservation of the BTLA-HVEM interaction between mouse and human suggests that this system is an important pathway regulating lymphocyte activation and/or homeostasis in the immune response.

Lymphotoxin and LIGHT signaling pathways and target genes.

Lymphotoxins (LT alpha and LT beta), LIGHT [homologous to LT, inducible expression, competes with herpes simplex virus (HSV) glycoprotein D for HSV entry mediator (HVEM), a receptor expressed on T lymphocytes], tumor necrosis factor (TNF), and their specific receptors LT beta R, HVEM, and TNF receptor 1 (TNFR1) and TNFR2, form the immediate family of the larger TNF superfamily. These cytokines establish a critical communication system required for the development of secondary lymphoid tissues; however, knowledge of the target genes activated by these signaling pathways is limited. Target genes regulated by the LT alpha beta-LT beta R pathway include the tissue-organizing chemokines, CXCL13, CCL19, and CCL21, which establish cytokine circuits that regulate LT expression on lymphocytes, leading to organized lymphoid tissue. Infectious disease models have revealed that LT alpha beta pathways are also important for innate and adaptive immune responses involved in host defense. Here, regulation of interferon-beta by LT beta R and TNFR signaling may play a crucial role in certain viral infections. Regulation of autoimmune regulator in the thymus via LT beta R implicates LT/LIGHT involvement in central tolerance. Dysregulated expression of LIGHT overrides peripheral tolerance leading to T-cell-driven autoimmune disease. Blockade of TNF/LT/LIGHT pathways as an intervention in controlling autoimmune diseases is attractive, but such therapy may have risks. Thus, identifying and understanding the target genes may offer an opportunity to fine-tune inhibitory interventions.

Scale-up of the fermentation and purification of the recombinant heavy chain fragment C of botulinum neurotoxin serotype F, expressed in Pichia pastoris.

A recombinant heavy chain fragment C of botulinum neurotoxin serotype F (BoNTF(Hc)) has been expressed in Pichia pastoris for use as an antigen in a proposed human vaccine. P. pastoris cells were grown using glycerol batch, glycerol fed-batch, and methanol fed-batch methods to achieve high cell densities. The total cellular protein recovered after homogenization was 72 mg/g of cell paste. BoNTF(Hc) was purified from soluble Pichia cell lysate employing ion-exchange chromatographic (IEC) and hydrophobic interaction chromatographic (HIC) methods developed at the bench scale using 10-100 mL columns. The process was performed at the pilot scale using 1-4L columns for evaluation of scale up. The purification process resulted in greater than 98% pure product consisting of at least three forms of BoNTF(Hc) based on mass spectrometry and yielded up to 205 mg/kg cells at the bench scale and 170 mg/kg cells at the pilot scale. Full-length BoNTF(Hc) is present based on mass spectrometry and SDS-PAGE, however is postulated to be N-terminally blocked by acetylation. N-terminal sequencing showed that two of the three forms are missing the first 11 (80%) and 14 (20%) amino acids of the N-terminus from the full-length form. The ratios of the two clipped forms were consistent from the bench to pilot scales. Purified BoNTF(Hc) at the pilot scale was found to sufficiently protect mice against a high dose of BoNTF neurotoxin.

Pichia pastoris fermentation with mixed-feeds of glycerol and methanol: growth kinetics and production improvement.

Fed-batch fermentation of a methanol utilization plus (Mut(+)) Pichia pastoris strain typically has a growth phase followed by a production phase (induction phase). In the growth phase glycerol is usually used as carbon for cell growth while in the production phase methanol serves as both inducer and carbon source for recombinant protein expression. Some researchers employed a mixed glycerol-methanol feeding strategy during the induction phase to improve production, but growth kinetics on glycerol and methanol and the interaction between them were not reported. The objective of this paper is to optimize the mixed feeding strategy based on growth kinetic studies using a Mut(+) Pichia strain, which expresses the heavy-chain fragment C of botulinum neurotoxin serotype C [BoNT/C(Hc)] intracellularly, as a model system. Growth models on glycerol and methanol that describe the relationship between specific growth rate ( micro ) and specific glycerol/methanol consumption rate ( nu(gly), nu(MeOH)) were established. A mixed feeding strategy with desired micro (gly)/ micro (MeOH) =1, 2, 3, 4 (desired micro (MeOH) set at 0.015 h(-1)) was employed to study growth interactions and their effect on production. The results show that the optimal desired micro (gly)/ micro (MeOH) is around 2 for obtaining the highest BoNT/C(Hc) protein content in cells: about 3 mg/g wet cells.