The Role of Spirochetes in Periodontal Disease

The spirochetal accumulation in subgingival plaque appears to be a function of the clinical severity of periodontal disease. It is not known how many different spirochetal species colonize the plaque, but based upon size alone, there are small, intermediate-sized, and large spirochetes. Four species of small spirochetes are cultivable, and of these, T. denticola has been shown to possess proteolytic and keratinolytic enzymes as well as factors or mechanisms which suppress lymphocyte blastogenesis and inhibit fibroblast and polymorphonuclear leukocyte (PMNL) function. All of these attributes could contribute to periodontal tissue insult. Yet independent of these potential virulence mechanisms, the overgrowth of spirochetes can be clinically useful if simply interpreted as indicating the result of tissue damage. In this case, the spirochetes would be indicators of disease and could be easily monitored by microscopic examination of plaque, or possibly by the measurement of benzoyl-DL-arginine-2-naphthylamide (BANA) hydrolytic activity in the plaque.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68092/2/10.1177_08959374880020021201.pd

Epigenetic Dysregulation of the Drp1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension: Mechanistic and Therapeutic Implications

Background -Mitotic fission is increased in pulmonary arterial hypertension (PAH), a hyperproliferative, apoptosis-resistant disease. The fission mediator, dynamin related protein 1 (Drp1) must complex with adaptor proteins to cause fission. Drp1-induced fission has been therapeutically targeted in experimental PAH. Here we examine the role of two recently discovered, poorly understood, Drp1 adapter proteins, mitochondrial dynamics protein of 49 and 51 kDa (MiD49 and MiD51) in normal vascular cells and explore their dysregulation in PAH. Methods -Immunoblots of pulmonary artery smooth muscle cells (PASMC, control, n=6; PAH, n=8) and immunohistochemistry of lung sections (control, n=6; PAH, n=6) were used to assess the expression of MiD49 and MiD51. The effects of manipulating MiDs on cell proliferation, cell cycle, and apoptosis were assessed in human and rodent PAH PASMC using flow cytometry. Mitochondrial fission was studied by confocal imaging. A microRNA (miR) involved in the regulation of MiD expression was identified using microarray techniques andin silicoanalyses. The expression of circulatory miR was assessed using qRT-PCR in healthy volunteers (HV) vs PAH patients from Sheffield, UK (plasma, HV, n=29, PAH, n=27; whole blood, HV, n=11, PAH, n=14), and then confirmed in a cohort from Beijing, China (plasma, HV, n=19, PAH, n=36; whole blood, HV, n=20, PAH, n=39). This work was replicated in monocrotaline and SU5416-hypoxia, preclinical PAH models. siRNA targeting MiDs or a miR mimic were nebulized to rats with monocrotaline-induced PAH (n=4-10). Results -MiD expression is increased in PAH PASMC, which accelerates Drp1-mediated mitotic fission, increases cell proliferation and decreases apoptosis. Silencing MiDs (but not other Drp1 binding partners, Fis1 or MFF) promotes mitochondrial fusion and causes G1-phase cell cycle arrest, through ERK1/2 and CDK4-dependent mechanism. Augmenting MiDs in normal cells causes fission and recapitulates the PAH phenotype. MiD upregulation results from decreased miR-34a-3p expression. Circulatory miR-34a-3p expression is decreased in both PAH patients and in preclinical models of PAH. Silencing MiDs or augmenting miR-34a-3p regresses experimental PAH. Conclusions -In health, MiDs regulate Drp1-mediated fission whilst in disease, epigenetic upregulation of MiDs increases mitotic fission, which drives pathologic proliferation and apoptosis resistance. The miR-34a-3p-MiD pathway offers new therapeutic targets for PAH

Temporal, spatial, and structural patterns of adult trembling aspen and white spruce mortality in Quebec's boreal forest

Temporal, spatial, and structural patterns of adult trembling aspen (Populus tremuloides Michx.) and white spruce (Picea glauca (Moench) Voss) mortality were studied in intact 150-year-old stands in the southwestern boreal forest of Quebec. For both species, mortality decreases (number of dead trees/total number of trees) with distance from the lake edge until 100-150 m, from which point it slightly increases. Strong peaks in mortality were found for 40- to 60-year-old aspen mainly between 1974 and 1992. Such mortality in relatively young aspen is likely related to competition for light from the dominant canopy trees. Also, the recruitment of this young aspen cohort is presumably the result of a stand breakup that occurred when the initial aspen-dominated stand was between 90 and 110 years old. For spruce, strong peaks in mortality were found in 110- to 150-year-old trees and they occurred mainly after 1980. No clear explanation could be found for these peaks, but we suggest that they may be related to senescence or weakening of the trees following the last spruce budworm outbreak. Suppressed and codominant aspen had a much higher mortality ratio than spruce in the same height class, while more surprisingly, no difference in mortality rate was found between dominant trees of the two species. Most spruce trees were found as standing dead, which leads us to reject the hypothesis that windthrow is an important cause of mortality for spruce in our forests

Low birth rates and reproductive skew limit the viability of Europe's captive eastern black rhinoceros, Diceros bicornis michaeli

Ex situ populations play a critical role for the conservation of endangered species, especially where in situ populations face imminent threats. For such populations to act as vital reserves, they must be viable and sustainable. Eastern black rhinoceros (Diceros bicornis michaeli) epitomise the delicate nature of conservation, as a steady increase in the in situ population over the last two decades is threatened to reverse due to intense poaching pressures on rhinoceros across sub-Saharan Africa. This study utilized population viability analysis to evaluate the demographic and genetic viability of the European captive population of eastern black rhinoceros, and compared demographic parameters to in situ reference populations. Although self-sustaining, the ex situ population performs poorly relative to in situ counterparts, growing at a rate of only 1–2 % per annum compared to 6–8 % for managed wild populations. Captive females start reproducing later, have longer inter-calving intervals, and a lower proportion breed each year. Furthermore, over 40 % of reproductive-age animals have yet to reproduce, with additional implications for the maintenance of genetic diversity. Pedigree analysis highlights the unequal contribution of wild-caught founders to the current population; 69 % of which have no living descendants, and more than a third of the current population are related to five founders. This results in a current genome equivalent of just 13.39 equally reproducing founders. Although reproductive skew is not unusual in wild populations, it severely undermines efforts to maintain genetic and phenotypic diversity in captive breeding programmes. We suggest that understanding and alleviating the causes of reproductive skew must be an important consideration for small population management to maintain the genetic and demographic viability of ex situ populations. © 2015, Springer Science+Business Media Dordrecht

Episodic Accretion in Young Stars

In the last twenty years, the topic of episodic accretion has gained significant interest in the star formation community. It is now viewed as a common, though still poorly understood, phenomenon in low-mass star formation. The FU Orionis objects (FUors) are long-studied examples of this phenomenon. FUors are believed to undergo accretion outbursts during which the accretion rate rapidly increases from typically 10 127 to a few 10 124 M 99 yr 121 , and remains elevated over several decades or more. EXors, a loosely defined class of pre-main sequence stars, exhibit shorter and repetitive outbursts, associated with lower accretion rates. The relationship between the two classes, and their connection to the standard pre-main sequence evolutionary sequence, is an open question: do they represent two distinct classes, are they triggered by the same physical mechanism, and do they occur in the same evolutionary phases? Over the past couple of decades, many theoretical and numerical models have been developed to explain the origin of FUor and EXor outbursts. In parallel, such accretion bursts have been detected at an increasing rate, and as observing techniques improve each individual outburst is studied in increasing detail. We summarize key observations of pre-main sequence star outbursts, and review the latest thinking on outburst triggering mechanisms, the propagation of outbursts from star/disk to disk/jet systems, the relation between classical EXors and FUors, and newly discovered outbursting sources \u2013 all of which shed new light on episodic accretion. We finally highlight some of the most promising directions for this field in the near- and long-term

Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage

Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored red blood cell units is clinically relevant for transfused recipients. Leukoreduced red blood cells from glucose- 6-phosphate dehydrogenase-normal or-deficient human volunteers were stored in AS-3 under normoxic, hyperoxic, or hypoxic conditions (with oxygen saturation ranging from <3% to >95%). Red blood cells from healthy human volunteers were also collected at sea level or after 1-7 days at high altitude (>5000 m). Finally, C57BL/6J mouse red blood cells were incubated in vitro with 13 C 1 -aspartate or 13 C 5 -adenosine under normoxic or hypoxic conditions, with or without deoxycoformycin, a purine deaminase inhibitor. Metabolomics analyses were performed on human and mouse red blood cells stored for up to 42 or 14 days, respectively, and correlated with 24 h post-transfusion red blood cell recovery. Hypoxanthine increased in stored red blood cell units as a function of oxygen levels. Stored red blood cells from human glucose-6-phosphate dehydrogenase-deficient donors had higher levels of deaminated purines. Hypoxia in vitro and in vivo decreased purine oxidation and enhanced purine salvage reactions in human and mouse red blood cells, which was partly explained by decreased adenosine monophosphate deaminase activity. In addition, hypoxanthine levels negatively correlated with post-transfusion red blood cell recovery in mice and – preliminarily albeit significantly- in humans. In conclusion, hypoxanthine is an in vitro metabolic marker of the red blood cell storage lesion that negatively correlates with post-transfusion recovery in vivo. Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates. © 2018 Ferrata Storti Foundation