POTENTIALLY UNLIMITED MULTIPLICATION OF YEAST WITH CONSTANT ENVIRONMENT,AND THE LIMITING OF GROWTH BY CHANGING ENVIRONMENT

1. The decrease in the rate of growth of a population of yeast cells, which results in the maintenance of an equilibrium crop level, is shown to be due to substances excreted into the culture medium by the growing cells. These toxic substances tend to destroy the young buds, because the percentage of budding cells is about the same at the time of most rapid growth and at the time of the growth equilibrium. 2. Alcohol is the product which primarily causes the decline of the growth rate. For the strain of yeast used, under the particular conditions of these experiments, a concentration of alcohol of about 1 mg. per cc. is associated with the beginning of the decrease of the growth rate. 3. The increasing acidity of the medium, due to CO₂, pyruvic acid, and other organic acids, is also a retarding influence. It is a secondary factor, however, as the greatest increase of the acidity of the medium occurs after pyruvic acid, probably a by-product of alcoholic fermentation, appears. 4. When the medium is maintained effectively constant, by preventing the accumulation of these toxic products, the yeast grows at a constant rate and the yeast growth is potentially unlimited. The limit of growth found in actual experiments is due only to the size of the test-tubes and to the relative efficiency of the method used in keeping the medium effectively constant. The necessity of maintaining a constant rate of growth in studies on the relations of yeasts to vitamines and other products is stressed.     

Lineages,splits and divergence challenge whether the terms anagenesis and cladogenesis are necessary

Using the framework of evolutionary lineages to separate the process of evolution and classification of species, we observe that ‘anagenesis’ and ‘cladogenesis’ are unnecessary terms. The terms have changed significantly in meaning over time, and current usage is inconsistent and vague across many different disciplines. The most popular definition of cladogenesis is the splitting of evolutionary lineages (cessation of gene flow), whereas anagenesis is evolutionary change between splits. Cladogenesis (and lineage‐splitting) is also regularly made synonymous with speciation. This definition is misleading as lineage‐splitting is prolific during evolution and because palaeontological studies provide no direct estimate of gene flow. The terms also fail to incorporate speciation without being arbitrary or relative, and the focus upon lineage‐splitting ignores the importance of divergence, hybridization, extinction and informative value (i.e. what is helpful to describe as a taxon) for species classification. We conclude and demonstrate that evolution and species diversity can be considered with greater clarity using simpler, more transparent terms than anagenesis and cladogenesis. Describing evolution and taxonomic classification can be straightforward, and there is no need to ‘make words mean so many different things’.     

Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus

The unexpected emergence of pandemic H1N1 influenza has generated significant interest in understanding immunological memory to influenza and how previous encounters with seasonal strains influence our ability to respond to novel strains. In this study, we evaluate the memory T cell repertoire in healthy adults to determine the abundance and protein specificity of influenza-reactive CD4 T cells, using an unbiased and empirical approach, and assess the ability of CD4 T cells to recognize epitopes naturally generated by infection with pandemic H1N1 virus. Our studies revealed that most individuals have abundant circulating CD4 T cells that recognize influenza-encoded proteins and that a strikingly large number of CD4 T cells can recognize autologous cells infected with live H1N1 virus. Collectively, our results indicate that a significant fraction of CD4 T cells generated from priming with seasonal virus and vaccines can be immediately mobilized upon infection with pandemic influenza strains derived from antigenic shift.     

The Longue Durée of genetic ancestry: multiple genetic marker systems and Celtic origins on the Atlantic facade of Europe

Celtic languages are now spoken only on the Atlantic facade of Europe, mainly in Britain and Ireland, but were spoken more widely in western and central Europe until the collapse of the Roman Empire in the first millennium a.d. It has been common to couple archaeological evidence for the expansion of Iron Age elites in central Europe with the dispersal of these languages and of Celtic ethnicity and to posit a central European "homeland" for the Celtic peoples. More recently, however, archaeologists have questioned this "migrationist" view of Celtic ethnogenesis. The proposition of a central European ancestry should be testable by examining the distribution of genetic markers; however, although Y-chromosome patterns in Atlantic Europe show little evidence of central European influence, there has hitherto been insufficient data to confirm this by use of mitochondrial DNA (mtDNA). Here, we present both new mtDNA data from Ireland and a novel analysis of a greatly enlarged European mtDNA database. We show that mtDNA lineages, when analyzed in sufficiently large numbers, display patterns significantly similar to a large fraction of both Y-chromosome and autosomal variation. These multiple genetic marker systems indicate a shared ancestry throughout the Atlantic zone, from northern Iberia to western Scandinavia, that dates back to the end of the last Ice Age.     

Health and Human Rights in Karen State,Eastern Myanmar

Background

Decades of conflict in eastern Myanmar have resulted in high prevalence of human rights violations and poor health outcomes. While recent ceasefire agreements have reduced conflict in this area, it is unknown whether this has resulted in concomitant reductions in human rights violations.

Methods and Findings

We conducted a two-stage cluster survey of 686 households in eastern Myanmar to assess health status, access to healthcare, food security, exposure to human rights violations and identification of alleged perpetrators over the 12 months prior to January 2012, a period of near-absence of conflict in this region. Household hunger (FANTA-2 scale) was moderate/high in 91 (13.2%) households, while the proportion of households reporting food shortages in each month of 2011 ranged from 19.9% in December to 47.0% in September, with food insecurity peaking just prior to the harvest. Diarrhea prevalence in children was 14.2% and in everyone it was 5.8%. Forced labor was the most common human rights violation (185 households, 24.9%), and 210 households (30.6%) reported experiencing one or more human rights violations in 2011. Multiple logistic regression analysis identified associations between human rights violations and poor health outcomes.

Conclusion

Human rights violations and their health consequences persist despite reduced intensity of conflict in eastern Myanmar. Ceasefire agreements should include language that protects human rights, and reconciliation efforts should address the health consequences of decades of human rights violations.     

IL-15 can signal via IL-15Rα, JNK, and NF-κB to drive RANTES production by myeloid cells

IL-15 plays many important roles within the immune system. IL-15 signals in lymphocytes via trans presentation, where accessory cells such as macrophages and dendritic cells present IL-15 bound to IL-15Rα in trans to NK cells and CD8(+) memory T cells expressing IL-15/IL-2Rβ and common γ chain (γ(c)). Previously, we showed that the prophylactic delivery of IL-15 to Rag2(-/-)γ(c)(-/-) mice (mature T, B, and NK cell negative) afforded protection against a lethal HSV-2 challenge and metastasis of B16/F10 melanoma cells. In this study, we demonstrated that in vivo delivery of an adenoviral construct optimized for the secretion of human IL-15 to Rag2(-/-)γ(c)(-/-) mice resulted in significant increases in spleen size and cell number, leading us to hypothesize that IL-15 signals differently in myeloid immune cells compared with lymphocytes, for which IL-15/IL-2Rβ and γ(c) expression are essential. Furthermore, treatment with IL-15 induced RANTES production by Rag2(-/-)γ(c)(-/-) bone marrow cells, but the presence of γ(c) did not increase bone marrow cell sensitivity to IL-15. This IL-15-mediated RANTES production by Rag2(-/-)γ(c)(-/-) bone marrow cells occurred independently of the IL-15/IL-2Rβ and Jak/STAT pathways and instead required IL-15Rα signaling as well as activation of JNK and NF-κB. Importantly, we also showed that the trans presentation of IL-15 by IL-15Rα boosts IL-15-mediated IFN-γ production by NK cells but reduces IL-15-mediated RANTES production by Rag2(-/-)γ(c)(-/-) myeloid bone marrow cells. Our data clearly show that IL-15 signaling in NK cells is different from that of myeloid immune cells. Additional insights into IL-15 biology may lead to novel therapies aimed at bolstering targeted immune responses against cancer and infectious disease.