Buffering effect of a prophylactic gel on dental plaque in institutionalised elderly

Objectives: The effect of multiple daily applications of a prophylactic gel, with buffering substances, on plaque acidogenicity in elderly institutionalised individuals was evaluated. Background: Many elderly suffer from reduced salivary flow, poor oral hygiene and increased levels of cariogenic bacteria and are considered to be at an increased risk for coronal and root caries. Reinforcing the buffering capacity of dental plaque by the addition of substances such as bicarbonate and phosphates may decrease their caries activity. Materials and methods: Fourteen elderly, with subjective dry mouth, were treated for 16‐day‐periods at random with: (i) Profylin fluoride gel with buffering components; (ii) Profylin fluoride gel without buffering components and (iii) rinsing with water. Applications were made four times a day and each period was followed by a 2‐week wash‐out period. The plaque pH was registered after a carbohydrate challenge and the following were recorded before and after each test period: stimulated salivary secretion rate, buffer capacity, number Colony Farming Units (CFU) mutans streptococci, lactobacilli and a sample of Candida albicans on oral mucosa. Results: Eleven participants (mean age 76.6 years) fulfilled the study. Changes in plaque pH measurements, when calculated as area under the curve (AUC_6.2 and AUC_5.7) values (pH × min), before and after each of the three treatments, showed no significant differences. A tendency to a higher plaque acidogenicity and amount of cariogenic microorganisms was found after the gel treatments. C. albicans was found in low levels. Conclusion: Frequent applications of the gel did not result in an improved neutralising effect in the elderly. This may be caused by a combination of several factors, such as the level of oral dryness of the individuals and low solubility, release and retention of the gel substances in plaque. Instead, an increased plaque acidogenicity was noted.     

A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation loop 3 (residues 365-374{216-225}) of the so-called activation domain and the 170-loop (residues 313-322{170A-175}) succeeding the TF-binding helix. The latter finding is corroborated by experiments demonstrating rapid deglycosylation of Asn322 in free FVIIa by PNGase F but almost complete protection in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S(1) and S(3) substrate pockets, the activation pocket, and N-terminal insertion.     

Stabilization of population fluctuations due to cannibalism promotes resource polymorphism in fish

Resource polymorphism is a well-known phenomenon in many taxa, assumed to be a consequence of strong competition for resources and to be facilitated by stable environments and the presence of several profitable resources on which to specialize. In fish, resource polymorphism, in the form of planktivore-benthivore pairs, is found in a number of species. We gathered literature data on life-history characteristics and population dynamics for 15 fish species and investigated factors related to the presence of such resource polymorphism. This investigation indicated that early cannibalism and low overall population variability are typically associated with the presence of resource polymorphism. These findings match previously reported patterns of population dynamics for size-structured fish populations, whereby early cannibalism has been shown to decrease temporal variation in population dynamics and to equalize the profitability of the zooplankton and macroinvertebrate resources. Our study suggests that competition alone is not a sufficient condition for the development of resource polymorphism because overly strong competition is typically associated with increased temporal variation (environmental instability). We conclude that although resource competition is an important factor regulating the development of resource polymorphism, cannibalism may also play a fundamental role by dampening population oscillations and possibly by equalizing the profitability of different resources.     

Construction of polyamine-modified uridine and adenosine derivatives--evaluation of DNA binding capacity and cytotoxicity in vitro

We here report the synthesis of the two polyamine-based nucleoside derivatives 5-{[bis-(3-aminopropyl)amino]acetamido-1-propynyl}uridine and 2-{[bis-(3-aminopropyl)amino]-acetamido-1-propynyl}adenosine. The various polyamine derivatives have been used in thermal melting analysis using DNA from herring testes, and in cellular studies using four different cell lines. The compounds were all found to be non-toxic, thus holding good promise for future use as siRNA building blocks.     

The Indignity of Relative Concepts of Animal Dignity: A Qualitative Study of People Working with Nonhuman Animals

The Swiss animal welfare legislation is considered to be one of the strictest such laws worldwide. One unique feature is the inclusion of the concept of “dignity of the creature” and, more precisely, animal dignity. We interviewed 19 people from Switzerland and Germany about their concepts of animal dignity. Thereby, we investigated whether the very specific concept of the Swiss law is reflected in the minds of those who work with nonhuman animals on a daily basis. The results of our qualitative interviews revealed an awareness of the legal term among Swiss interviewees, but their personal concepts of animal dignity were not based on or similar to the legal definitions. The interviewed participants presented a broad range of concepts, including: similarities to human dignity, replacing concepts such as respect or integrity, and context-dependent, contingent forms of dignity. The applicability or usefulness of animal dignity was questioned by several participants; many judged it to be confusing or difficult. Therefore, we conclude by discussing animal integrity as an alternative concept that reflects the interviewees’ ideas of treating nonhuman animals in a respectful and appropriate way, and at the same time does not have the strongly metaphysical connotations of a concept such as human dignity.     

Organic farming increases richness of fungal taxa in the wheat phyllosphere

Organic farming is often advocated as an approach to mitigate biodiversity loss on agricultural land. The phyllosphere provides a habitat for diverse fungal communities that are important for plant health and productivity. However, it is still unknown how organic farming affects the diversity of phyllosphere fungi in major crops. We sampled wheat leaves from 22 organically and conventionally cultivated fields in Sweden, paired based on their geographical location and wheat cultivar. Fungal communities were described using amplicon sequencing and real‐time PCR. Species richness was higher on wheat leaves from organically managed fields, with a mean of 54 operational taxonomic units (OTUs) compared with 40 OTUs for conventionally managed fields. The main components of the fungal community were similar throughout the 350‐km‐long sampling area, and seven OTUs were present in all fields: Zymoseptoria, Dioszegia fristingensis, Cladosporium, Dioszegia hungarica, Cryptococcus, Ascochyta and Dioszegia. Fungal abundance was highly variable between fields, 10³–10⁵ internal transcribed spacer copies per ng wheat DNA, but did not differ between cropping systems. Further analyses showed that weed biomass was the strongest explanatory variable for fungal community composition and OTU richness. These findings help provide a more comprehensive understanding of the effect of organic farming on the diversity of organism groups in different habitats within the agroecosystem.     

Glutamate decarboxylase (GAD) autoantibody epitope shift during the first year of type 1 diabetes.

Autoantibodies in Type 1 diabetes patients may differentiate between glutamate decarboxylase (GAD65) cloned from human, mouse and rat with a significant better binding to the human antigen. A subgroup of 15% (27/183) patients showed significantly better binding to rodent than to human GAD65. The aim of this study was to determine whether the autoantibody specificity would remain anti-rodent during longitudinal follow-up for one year. We observed 1) that the average slope of the difference between human and mouse GAD65 autoantibodies binding increased between onset and after one year, which demonstrates reduced binding to rodent GAD65 and 2) that, in a group followed every third month, 9/11 (80%) children with rodent specific GAD65 autoantibodies at onset converted within one year to preference against human GAD65. This shift in preference was confirmed by significantly lower EC50 values in the initially anti-rodent GAD65 autoantibodies compared to samples taken one year after clinical diagnosis as determined in displacement studies with unlabeled human GAD65. We speculate that the evolution of GAD65 autoantibodies in Type 1 diabetes includes reactivity to a non-human GAD65 N-terminal end conformation. Progression towards Type 1 diabetes is, however, associated with a maturation of the immune response towards human GAD65 autoreactivity.     

Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus

At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.     

Dinoflagellate gamete formation and environmental cues: Observations, theory, and synthesis

For some species of cyst-producing dinoflagellates, the sexual life cycle is well studied in laboratory cultures. Dinoflagellate blooms in stratified waters, vertical migration of vegetative cells, and the accumulation of populations within thin layers are well-documented phenomena in nature. We propose a conceptual model that places these phenomena in a functional, ecological context: vegetative cells of a dinoflagellate population display vertical migration, but at the end of the bloom, environmental or internal cues shift the cell cycle to gamete formation. Then the vertical migrations cease, and cells accumulate in a layer at the pycnocline where gametes fuse to form zygotes, which then sink to the sediment as resting cysts. We support this conceptual model with experimental and environmental evidence.