Comparative Genomics of Bordetella pertussis Reveals Progressive Gene Loss in Finnish Strains

BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations

Relationships of dietary patterns with body composition in older adults differ by gender and PPAR-γ Pro12Ala genotype

Dietary patterns may better capture the multifaceted effects of diet on body composition than individual nutrients or foods. The objective of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with body composition. The influence of a polymorphism in the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene was considered. The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3,075 older adults. Participants’ body composition and genetic variation were measured in detail. Food intake was assessed with a semi-quantitative food frequency questionnaire (Block Dietary Data Systems, Berkeley, CA), and dietary patterns of 1,809 participants with complete data were derived by cluster analysis. Six clusters were identified, including a ‘Healthy foods’ cluster characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. An interaction was found between dietary patterns and PPAR-γ Pro12Ala genotype in relation to body composition. While Pro/Pro homozygous men and women in the ‘Healthy foods’ cluster did not differ significantly in body composition from those in other clusters, men with the Ala allele in the ‘Healthy foods’ cluster had significantly lower levels of adiposity than those in other clusters. Women with the Ala allele in the ‘Healthy foods’ cluster differed only in right thigh intermuscular fat from those in other clusters. Relationships between diet and body composition in older adults may differ by gender and by genetic factors such as PPAR-γ Pro12Ala genotype

Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay

BACKGROUND: In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD) plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate. RESULTS: In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs). Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1`s role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3` UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms. CONCLUSIONS: Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Education, Work and Life

In this chapter, I will study the relationship between education and working life from a few viewpoints. First, I will examine how everyday working life has changed and how education has to change. Second, I will depict how the practices of both education and the working world can and should be researched in terms of the theory of practice architectures. Third, I will come back to reflect on the relationships between work, education and life. The work that people do has increasingly been immaterialized. Working life has been detached from material production which is more and more automated and robotically driven. According to a Swiss professor Schwab (2015, 2016), we have already moved into a new era that can be called the fourth industrial revolution . The emerging and partially ongoing new revolution is speeded up by new technological breakthroughs in quantum computing , nano-technology , gene-technology , additive manufacturing (AM), Internet of things (IoT) and synthetic biology. All these innovations, mingled with each other, fundamentally change our lives on Earth. At the core of the fourth industrial revolution and society are the cognitive skills of humans. This new order of economy can called cognitive capitalism or cognitive economy . Consequently, cognitive work is ever present in our lives. The work we do every day is technically with us everywhere, so we can colloquially call it anyplace working . Because cognitive work is essentially learning, we may say that learning also becomes anyplace learning . In other words, the development of cognitive skills is actively supported not only in formal education but also in nonformal and informal settings. This scenario leads to societal polarization : the divide into the ‘haves’ and the ‘have-nots’. As the borders between professions fade away, new jobs are created. These new kinds of jobs are hybrid jobs. Thus, we may find an ongoing process of hybridization in working life. The group of short-term workers, some doing fairly demanding assignments, have received the unifying title of the precariat. It is an ironic play on words, combining the old working class-term, proletariat with the French word précarité (Eng. precarious), that signifies uncertainty, instability and a high risk factor. In other work, working life today is becoming precarisized. To summarize, the ongoing tendencies of work and working life can be fused into nine intertwined core concepts. Firstly, the processes of work have undergone processes of immaterialization, digization , robotization and globalization . Secondly, and partially as a consequence of the previous processes, the processes of learning at work and for work have undergone elliptical processes of formalization of informal learning and informalization of formal education. All these have consequences for the work force in the forms of polarization , hybridization and precarization . These tendencies can be labelled under the umbrella term of new work . The practices of working life have dramatically merged, and new kinds of research are needed so as to better understand reasons why practices are as they are. In order to understand practices of new work, we need knowledge about: (1) economic resources or physical and material routines, habits of action and activities which prefigure social practices; (2) how practices of new work are understood and discursively formed by using cultural symbols, words, concepts and discourses; and (3) social and political relations which are prefigured through power and solidarity as well as processes of indoctrination, oppression and emancipation from coercive power. To put it briefly, in order to understand how practices are possible and how it is possible to change practices, we need research on (1) material-economic (2) cultural-discursive as semantic, as well as (3) social-political prerequisites of practices.peerReviewe