Population Genetics Of Borrelia Burgdorferi In The Eastern And Midwestern United States

Changes in climate and land-use are influencing the spatial distributions and population structure of species throughout the world. Among those species predicted to be affected by changes in climate and land-use are the hosts and vectors of many zoonotic pathogens, including the hosts and vectors of the Lyme borreliosis pathogen, Borrelia burgdorferi. In this study, we investigate the population structure of B. burgdorferi at the interface of two expanding vector populations using a population genetic and phylogeographic approach. We then examine the influence of recombination between major B. burgdorferi lineages on the population structure of B. burgdorferi within and between geographic regions. We found that B. burgdorferi lineages were heterogeneously distributed between the Northeast and Southeast United States, suggesting that gene flow between geographic regions is limited for some lineages while other lineages showed evidence of long distance dispersal. We identified at least two clonal B. burgdorferi lineages present in both competent vector species found in southern Virginia, suggesting that vector species is not a barrier to dispersal between regions. Population genetic and phylogeographic analyses of B. burgdorferi reveal a complicated pattern of population structure within and between geographic regions. Population genomic analyses show recombination between lineages despite evidence of strong linkage disequilibrium and a lack of genetic variation within B. burgdorferi lineages, suggesting a small effective population size

Yersinia pestis DNA from Skeletal Remains from the 6(th) Century AD Reveals Insights into Justinianic Plague.

Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics

Axonal Transport, Phase-Separated Compartments, and Neuron Mechanics - A New Approach to Investigate Neurodegenerative Diseases

Many molecular and cellular pathogenic mechanisms of neurodegenerative diseases have been revealed. However, it is unclear what role a putatively impaired neuronal transport with respect to altered mechanical properties of neurons play in the initiation and progression of such diseases. The biochemical aspects of intracellular axonal transport, which is important for molecular movements through the cytoplasm, e.g., mitochondrial movement, has already been studied. Interestingly, transport deficiencies are associated with the emergence of the affliction and potentially linked to disease transmission. Transport along the axon depends on the normal function of the neuronal cytoskeleton, which is also a major contributor to neuronal mechanical properties. By contrast, little attention has been paid to the mechanical properties of neurons and axons impaired by neurodegeneration, and of membraneless, phase-separated organelles such as stress granules (SGs) within neurons. Mechanical changes may indicate cytoskeleton reorganization and function, and thus give information about the transport and other system impairment. Nowadays, several techniques to investigate cellular mechanical properties are available. In this review, we discuss how select biophysical methods to probe material properties could contribute to the general understanding of mechanisms underlying neurodegenerative diseases

Dual Activation of Phospholipase C-ϵ by Rho and Ras GTPases

Phospholipase C-ε (PLC-ε) is a highly elaborated PLC required for a diverse set of signaling pathways. Here we use a combination of cellular assays and studies with purified proteins to show that activated RhoA and Ras isoforms directly engage distinct regions of PLC-ε to stimulate its phospholipase activity. Purified PLC-ε was activated in a guanine nucleotide- and concentration-dependent fashion by purified lipidated K-Ras reconstituted in PtdIns(4,5)P2-containing phospholipid vesicles. Whereas mutation of two critical lysine residues within the second Ras-association domain of PLC-ε prevented K-Ras-dependent activation of the purified enzyme, guanine nucleotide-dependent activation by RhoA was retained. Deletion of a loop unique to PLC-ε eliminated its activation by RhoA but not H-Ras. In contrast, removal of the autoinhibitory X/Y-linker region of the catalytic core of PLC-ε markedly activates the enzyme (Hicks, S. N., Jezyk, M. R., Gershburg, S., Seifert, J. P., Harden, T. K., and Sondek, J. (2008) Mol. Cell, 31, 383–394), but PLC-ε lacking this regulatory region retained activation by both Rho and Ras GTPases. Additive activation of PLC-ε by RhoA and K- or H-Ras was observed in intact cell studies, and this additivity was recapitulated in experiments in which activation of purified PLC-ε was quantified with PtdIns(4,5)P2-containing phospholipid vesicles reconstituted with purified, isoprenylated GTPases. A maximally effective concentration of activated RhoA also increased the sensitivity of purified PLC-ε to activation by K-Ras. These results indicate that PLC-ε can be directly and concomitantly activated by both RhoA and individual Ras GTPases resulting in diverse upstream control of signaling cascades downstream of PLC-ε

Розвиток закордонної релігійної періодики УАПЦ в екзилі на прикладі часопису «Життя і Церква» (The Development of Foreign Religious Periodicals of Ukrainian Autocephalous Orthodox Church in Exile on the Example of the Magazine Life and Church)

Тези присвячені історії української православної церкви закордоном. У центрі уваги – внутрішнє життя церкви, яке репрезентувалося на шпальтах релігійної періодики. На прикладі такого видання як «Життя і церква», з’ясовано інформаційне наповнення публікацій на сторінках подібних журналів. Різноплановий характер поданих у них відомостей є важливим джерелом до вивчення історії українського релігійного життя в діаспорі, особливостей церковного повсякдення. Вони також виступають ключем до розуміння методів збереження національної ідентичності та релігійної самобутності в чужому соціокультурному середовищі. (The author presents the history of the Ukrainian Orthodox Church abroad. The main attention is focused on the internal life of the church, that is represented on the pages of religious periodicals. Using the magazine Life and Church as an example, the author of the research illustrates the typicality of the content of such kind of a publication. Versatile character of the content is an important source to study the history of the Ukrainian religious life in the Diaspora, as well as the features of everyday life in church. They also act as a key to understanding the methods of preserving national and religious identity in another sociocultural environment.

Translational Evaluation of Acid/Base and Electrolyte Alterations in Rodent Model of Focal Ischemia

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion. METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient middle cerebral artery occlusion models. RESULTS: Analysis indicated significant differences in the blood gas and electrolytes between pre- to post-middle cerebral artery occlusion. A decrease in pH and sodium with increases in carbon dioxide, potassium, ionized calcium, and glucose changes were found in both middle cerebral artery occlusion models; while hematocrit and hemoglobin were significant in the transient model. pH and ionized calcium were predictors of infarct volume in the permanent model, as changes in pH and ionized calcium decreased, infarct volume increased. CONCLUSIONS: There are acute changes in acid/base balance and electrolytes during stroke in transient and permanent rodent models. Additionally, we found pH and ionized calcium changes predicted stroke volume in the permanent middle cerebral artery occlusion model. These preliminary findings are novel, and warrant further exploration in human conditions