Effects of aging on apoptosis gene expression in oral mucosal tissues

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca⁺²-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.     

Multispecies biofilms and host responses: “Discriminating the Trees from the Forest”

Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the three-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into these processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms.     

Warming up the system: higher predator feeding rates but lower energetic efficiencies

Predictions on the consequences of the rapidly increasing atmospheric CO₂ levels and associated climate warming for population dynamics, ecological community structure and ecosystem functioning depend on mechanistic energetic models of temperature effects on populations and their interactions. However, such mechanistic approaches combining warming effects on metabolic (energy loss of organisms) and feeding rates (energy gain by organisms) remain a key, yet elusive, goal. Aiming to fill this void, we studied the metabolic rates and functional responses of three differently sized, predatory ground beetles on one mobile and one more resident prey species across a temperature gradient (5, 10, 15, 20, 25 and 30 °C). Synthesizing metabolic and functional‐response theory, we develop novel mechanistic predictions how predator–prey interaction strengths (i.e., functional responses) should respond to warming. Corroborating prior theory, warming caused strong increases in metabolism and decreases in handling time. Consistent with our novel model, we found increases in predator attack rates on a mobile prey, whereas attack rates on a mostly resident prey remained constant across the temperature gradient. Together, these results provide critically important information that environmental warming generally increases the direct short‐term per capita interaction strengths between predators and their prey as described by functional‐response models. Nevertheless, the several fold stronger increase in metabolism with warming caused decreases in energetic efficiencies (ratio of per capita feeding rate to metabolic rate) for all predator–prey interactions. This implies that warming of natural ecosystems may dampen predator–prey oscillations thus stabilizing their dynamics. The severe long‐term implications; however, include predator starvation due to energetic inefficiency despite abundant resources.     

The Arctic Warbler Phylloscopus borealis– three anciently separated cryptic species revealed

The Arctic Warbler Phylloscopus borealis breeds across the northern Palaearctic and northwestern‐most Nearctic, from northern Scandinavia to Alaska, extending south to southern Japan, and winters in Southeast Asia, the Philippines and Indonesia. Several subspecies have been described based on subtle morphological characteristics, although the taxonomy varies considerably among different authors. A recent study (T. Saitoh et al. (2010) BMC Evol. Biol. 10 : 35) identified three main mitochondrial DNA clades, corresponding to: (1) continental Eurasia and Alaska, (2) south Kamchatka, Sakhalin and northeast Hokkaido, and (3) most of Japan (Honshu, Shikoku, Kyushu). These three clades were estimated to have diverged during the late Pliocene to early Pleistocene (border at c. 2.6 million years ago). Differences in morphometrics have also been reported among members of the three clades (T. Saitoh et al. (2008) Ornithol. Sci. 7 : 135–142). Here we analyse songs and calls from throughout the range of the Arctic Warbler, and conclude that these differ markedly and consistently among the populations representing the three mitochondrial clades. Kurile populations, for which no sequence data are available, are shown to belong to the second clade. To determine the correct application of available scientific names, mitochondrial DNA was sequenced from three name‐bearing type specimens collected on migration or in the winter quarters. Based on the congruent variation in mitochondrial DNA, morphology and vocalizations, we propose that three species be recognized: Arctic Warbler Phylloscopus borealis (sensu stricto) (continental Eurasia and Alaska), Kamchatka Leaf Warbler Phylloscopus examinandus (Kamchatka (at least the southern part), Sakhalin, Hokkaido and Kurile Islands), and Japanese Leaf Warbler Phylloscopus xanthodryas (Japan except Hokkaido).     

T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Introduction

A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.

Methods

In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and negative (IFN^-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow cytometry and compared between IFN⁺, IFN^- patients and HCs.

Results

Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ cells were observed in IFN⁺ patients compared with IFN^- patients and HCs. IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6⁺ cells.

Conclusions

We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.     

Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

Background

Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND.

Methods

Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing.

Results

Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree.

Conclusion

Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.