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The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer’s disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson’s disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.

Objective: To report our experience with 18F‐fluoro‐ethyl‐tyrosine (FET) positron emission tomography‐computed tomography (PET‐CT) co‐registered with magnetic resonance imaging (MRI) (FET‐PET/MRICR) in the care trajectory for persistent acromegaly. Design: Prospective case series. Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. Measurements: FET‐PET/MRICR was used to support decision‐making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. Results: FET‐PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET‐PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET‐PET/MRICR identified suggestive new foci in four other patients. Surgical re‐exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET‐PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF‐1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET‐PET/MRICR is a new tracer to provide additional information to aid decision‐making by the multidisciplinary pituitary team. [ABSTRACT FROM AUTHOR]

The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer's disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson's disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged. [ABSTRACT FROM AUTHOR]

It is well established that the herpesvirus nuclear egress complex (NEC) has an intrinsic ability to deform membranes. During viral infection, the membrane-deformation activity of the NEC must be precisely regulated to ensure efficient nuclear egress of capsids. One viral protein known to regulate herpes simplex virus type 2 (HSV-2) NEC activity is the tegument protein pUL21. Cells infected with an HSV-2 mutant lacking pUL21 (ΔUL21) produced a slower migrating species of the viral serine/threonine kinase pUs3 that was shown to be a hyperphosphorylated form of the enzyme. Investigation of the pUs3 substrate profile in ΔUL21-infected cells revealed a prominent band with a molecular weight consistent with that of the NEC components pUL31 and pUL34. Phosphatase sensitivity and retarded mobility in phos-tag SDS-PAGE confirmed that both pUL31 and pUL34 were hyperphosphorylated by pUs3 in the absence of pUL21. To gain insight into the consequences of increased phosphorylation of NEC components, the architecture of the nuclear envelope in cells producing the HSV-2 NEC in the presence or absence of pUs3 was examined. In cells with robust NEC production, invaginations of the inner nuclear membrane were observed that contained budded vesicles of uniform size. By contrast, nuclear envelope deformations protruding outwards from the nucleus, were observed when pUs3 was included in transfections with the HSV-2 NEC. Finally, when pUL21 was included in transfections with the HSV-2 NEC and pUs3, decreased phosphorylation of NEC components was observed in comparison to transfections lacking pUL21. These results demonstrate that pUL21 influences the phosphorylation status of pUs3 and the HSV-2 NEC and that this has consequences for the architecture of the nuclear envelope.

An outstanding challenge in modern society remains how to make crosslinked polymers (thermosets) more recyclable. A breakthrough solution to this challenge has been the introduction of dynamic covalent bonds in polymer networks, yielding covalent adaptable networks (CANs). Ongoing research is focused on finding new suitable dynamic covalent chemistries and on how to tune the material properties of CANs derived from these new chemistries. Here, we first compare two different dynamic boronic acid based covalent adaptable networks, namely, a conventional boronate‐diol and a novel boronate‐TetraAzaADamantane (TAAD) system. We show that incorporating boronate‐TAAD bonds in networks results in stiffer materials, as seen in a slower relaxation and higher shear and storage moduli. This offers access to more mechanically robust boronate‐based materials, compared to conventional boronate‐based gels. Next, we investigate the effect of molecular tuning via the electron density of meta‐positioned ring substituents on the macroscopic material properties for the boronate‐TAAD network. By comparing relaxation experiments on materials with different substituents, we show that the macroscopic network relaxation can be tuned through the Hammett parameter of the meta‐substituent and the activation energy of the boronate‐TAAD exchange. This enables subtle control over the (dynamic) material properties of these novel, robust boronate‐based networks. [ABSTRACT FROM AUTHOR]

In this synthesis article, I discuss the meaning of active citizenship for European nature conservation based on an integrative study of existing literature. Four main knowledge gaps are addressed: (1) a lack of overview on the scope and characteristics of active citizenship across Europe; (2) a lack of systematic evidence on its impacts; (3) a lack of congruence in democratic debates related to active citizenship; and (4) the governance implications of active citizenship in context of these knowledge gaps. Empirical research shows that active citizenship is driven by a wide range of motivations and manifests in various forms. Although most active citizenship is small in scale, when added together all these groups of citizens have become a societal force to be reckoned with. Locally, active citizenship often provides important benefits to people and nature and also enriches the democratic system. However, active citizenship does not always align with policy frameworks and ecological networks and also leads to tensions between representative and direct forms of democracy. For these reasons, active citizenship should be considered as additive to other forms of governance in European nature conservation. In this, a polycentric and collaborative approach to green space governance can help authorities in achieving their own policy objectives while stimulating active citizenship.

This paper presents the results of an exploration into the adoption of biodiversity-friendly practices by the real estate sector, by researching which factors determine companies’ intentions to use nature-inclusive design and construction concepts (NID). NID represents practices in which nature and building are inextricably linked when (re)designing building projects. We applied the Theory of Planned Behavior (TPB), a well-known framework for studying behavior. A telephone survey was carried out among 103 employees at different types of companies in the real estate sector. The findings showed that attitude, social norms, and perceived behavioral control are all significant explanatory variables for the intention of using NID. Perceived behavioral control is the strongest predictor. In addition, interest in NID strengthens the predictive value of perceived behavioral control. The empirical findings in this study serve as a first attempt to provide insights into the determinants of behavior in favor of using NID and, by extension, looking for drivers for change. The study was carried out in the Netherlands, but the results may be applicable or interesting to other countries as well when looking for opportunities to enhance biodiversity in urban areas or considering how the real estate sector could give substance to their vital role in spatial developments.

Abstract The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the herpesvirus nuclear egress complex that not only functions in the egress of DNA containing capsids from the nucleus, but is also required for optimal replication of viral DNA and its packaging into capsids. Here we report that the UL31 protein from HSV-2 can be recruited to sites of DNA damage by sequences found in its N-terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP-ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31 recruitment to damaged DNA. Whereas PAR polymerase inhibition prevented UL31 recruitment to damaged DNA, inhibition of signaling through the ataxia telangiectasia mutated DNA damage response pathway had no effect. These findings were further supported by experiments demonstrating direct and specific interaction between HSV-2 UL31 and PAR using purified components. This study reveals a previously unrecognized function for UL31 and may suggest that the recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus capsids, influences viral DNA replication and packaging, or possibly modulates the DNA damage response mounted by virally infected cells.

Currently, batch release of toxoid vaccines, such as diphtheria and tetanus toxoid, requires animal tests to confirm safety and immunogenicity. Efforts are being made to replace these tests with in vitro assays in a consistency approach. Limitations of current in vitro assays include the need for reference antigens and most are only applicable to drug substance, not to the aluminum adjuvant-containing and often multivalent drug product. To overcome these issues, a new assay was developed based on mimicking the proteolytic degradation processes in antigen-presenting cells with recombinant cathepsin S, followed by absolute quantification of the formed peptides by liquid chromatography-mass spectrometry. Temperature-exposed tetanus toxoids from several manufacturers were used as aberrant samples and could easily be distinguished from the untreated controls by using the newly developed degradomics assay. Consistency of various batches of a single manufacturer could also be determined. Moreover, the assay was shown to be applicable to Al(OH)3 and AlPO4-adsorbed tetanus toxoids. Overall, the assay shows potential for use in both stability studies and as an alternative for in vivo potency studies by showing batch-to-batch consistency of bulk toxoids as well as for aluminum-containing vaccines.

Therapeutic cancer vaccines trigger CD4 + and CD8 + T cell responses capable of established tumor eradication. Current platforms include DNA, mRNA and synthetic long peptide (SLP) vaccines, all aiming at robust T cell responses. SLPs linked to the Amplivant® adjuvant (Amplivant-SLP) have shown effective delivery to dendritic cells, resulting in improved immunogenicity in mice. We have now tested virosomes as a delivery vehicle for SLPs. Virosomes are nanoparticles made from influenza virus membranes and have been used as vaccines for a variety of antigens. Amplivant-SLP virosomes induced the expansion of more antigen-specific CD8 + T memory cells in ex vivo experiments with human PBMCs than Amplivant-SLP conjugates alone. The immune response could be further improved by including the adjuvants QS-21 and 3D-PHAD in the virosomal membrane. In these experiments, the SLPs were anchored in the membrane through the hydrophobic Amplivant adjuvant. In a therapeutic mouse model of HPV16 E6/E7+ cancer, mice were vaccinated with virosomes loaded with either Amplivant-conjugated SLPs or lipid-coupled SLPs. Vaccination with both types of virosomes significantly improved the control of tumor outgrowth, leading to elimination of the tumors in about half the animals for the best combinations of adjuvants and to their survival beyond 100 days. [ABSTRACT FROM AUTHOR]

Deficiency of α-galactosidase A (α-GAL) causes Fabry disease (FD), an X-linked storage disease of the glycosphingolipid globtriaosylcerammide (Gb3) in lysosomes of various cells and elevated plasma globotriaosylsphingosine (Lyso-Gb3) toxic for podocytes and nociceptive neurons. Enzyme replacement therapy is used to treat the disease, but clinical efficacy is limited in many male FD patients due to development of neutralizing antibodies (Ab). Therapeutic use of modified lysosomal α-N-acetyl-galactosaminidase (α-NAGAL) with increased α-galactosidase activity (α-NAGALEL) has therefore been suggested. We transiently produced in Nicotiana benthamiana leaves functional α-GAL, α-NAGAL, and α-NAGALEL enzymes for research purposes. All enzymes could be visualized with activity-based probes covalently binding in their catalytic pocket. Characterization of purified proteins indicated that α-NAGALEL is improved in activity toward artificial 4MU-α-galactopyranoside. Recombinant α-NAGALEL and α-NAGAL are not neutralized by Ab-positive FD serum tested and are more stable in human plasma than α-GAL. Both enzymes hydrolyze the lipid substrates Gb3 and Lyso-Gb3 accumulating in Fabry patients. The addition to FD sera of α-NAGALEL, and to a lesser extent that of α-NAGAL, results in a reduction of the toxic Lyso-Gb3. In conclusion, our study suggests that modified α-NAGALEL might reduce excessive Lyso-Gb3 in FD serum. This neo-enzyme can be produced in Nicotiana benthamiana and might be further developed for the treatment of FD aiming at reduction of circulating Lyso-Gb3.