Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation

Saccharomyces cerevisiae exhibits gene expression homeostasis, which is defined as the buffering of transcription levels against changes in DNA copy number during the S phase of the cell cycle. It has been suggested that S. cerevisiae employs an active mechanism to maintain gene expression homeostasis through Rtt109-Asf1-dependent acetylation of histone H3 on lysine 56 (H3K56). Here, we show that gene expression homeostasis can be achieved independently of H3K56 acetylation by Tos4 (Target of Swi6-4). Using Nanostring technology, we establish that Tos4-dependent gene expression homeostasis depends on its forkhead-associated (FHA) domain, which is a phosphopeptide recognition domain required to bind histone deacetylases (HDACs). We demonstrate that the mechanism of Tos4-dependent gene expression homeostasis requires its interaction with the Rpd3L HDAC complex. However, this is independent of Rpd3’s well-established roles in both histone deacetylation and controlling the DNA replication timing program, as established by deep sequencing of Fluorescence-Activated Cell Sorted (FACS) S and G2 phase populations. Overall, our data reveals that Tos4 mediates gene expression homeostasis through its FHA domain-dependent interaction with the Rpd3L complex, which is independent of H3K56ac

How the 'plates' of a health system can shift, change and adjust during economic recessions: A qualitative interview study of public and private health providers in Brazil's Sao Paulo and Maranhao states

Background: Economic recessions carry an impact on population health and access to care; less is known on how health systems adapt to the conditions brought by a downturn. This particularly matters now that the COVID-19 epidemic is putting health systems under stress. Brazil is one of the world’s most affected countries, and its health system was already experiencing the aftermath of the 2015 recession. Methods: Between 2018 and 2019 we conducted 46 semi-structured interviews with health practitioners, managers and policy-makers to explore the impact of the 2015 recession on public and private providers in prosperous (São Paulo) and impoverished (Maranhão) states in Brazil. Thematic analysis was employed to identify drivers and consequences of system adaptation and coping strategies. Nvivo software was used to aid data collection and analysis. We followed the Standards for Reporting Qualitative Research to provide an account of the findings. Results: We found the concept of ‘health sector crisis’ to be politically charged among healthcare providers in São Paulo and Maranhão. Contrary to expectations, the public sector was reported to have found ways to compensate for diminishing federal funding, having outsourced services and adopted flexible–if insecure–working arrangements. Following a drop in employment and health plans, private health insurance companies have streamlined their offer, at times at the expenses of coverage. Low-cost walk-in clinics were hit hard by the recession, but were also credited for having moved to cater for higher-income customers in Maranhão. Conclusions: The ‘plates’ of a health system may shift and adjust in unexpected ways in response to recessions, and some of these changes might outlast the crisis. As low-income countries enter post-COVID economic recessions, it will be important to monitor the adjustments taking place in health systems, to ensure that past gains in access to care and job security are not eroded

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Evaluating amplified rDNA restriction analysis assay for identification of bacterial communities

Amplified ribosomal DNA restriction analysis (ARDRA) and restriction fragment length polymorphism were originally used for strain typing and for screening clone libraries to identify phylogenetic clusters within a microbial community. Here we used ARDRA as a model to examine the capacity of restriction-based techniques for clone identification, and the possibility of deriving phylogenetic information from ARDRA-based dendrograms. ARDRA was performed in silico on 48,759 sequences from the Ribosomal Database Project, and it was found that the fragmentation profiles were not necessarily unique for each sequence in the database, resulting in different species sharing fragmentation profiles. Although ARDRA-based clusters separated clones into different genera, these phylogenetic clusters did not overlap with trees constructed according to sequence alignment, calling into question the intra-genus ARDRA-based phylogeny. It is thus suggested that the prediction power of ARDRA clusters in identifying clone phylogeny be regarded with caution

Combined Spatial Prediction of Schistosomiasis and Soil-Transmitted Helminthiasis in Sierra Leone: A Tool for Integrated Disease Control

Two forms of schistosomiasis or bilharzia (intestinal and urogenital) exist in Sierra Leone. The main control strategy for this disease currently is through mass drug administration (MDA) according to the World Health Organization recommended anthelminthic chemotherapy guidelines, and others include snail control, behavior change, and safe water, sanitation and hygiene. Survey on distribution and prevalence of the disease is vital to the planning of MDA in each district. The distribution of intestinal schistosomiasis in the country has been reported previously. The current national survey showed that urogenital schistosomiasis has a specific focal distribution particularly in the central and eastern regions of the country, most prevalent in Bo (24.6%), Koinadugu (20.4%) and Kono (25.3%) districts. Using a simple probabilistic model, this map was combined with the previously reported maps on intestinal schistosomiasis and the combined schistosomiasis prevalence was estimated. The combined schistosomiasis map highlights the presence of high-risk communities in an extensive area in the northeastern half of the country, which provides a tool for planning the national MDA activities

Glycoinositolphospholipids from Leishmania braziliensis and L. infantum: Modulation of Innate Immune System and Variations in Carbohydrate Structure

The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2−/− and TLR4−/−) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages

Understanding the adoption of business analytics and intelligence

Cruz-Jesus, F., Oliveira, T., & Naranjo, M. (2018). Understanding the adoption of business analytics and intelligence. In Á. Rocha, H. Adeli, L. P. Reis, & S. Costanzo (Eds.), Trends and Advances in Information Systems and Technologies, pp. 1094-1103. (Advances in Intelligent Systems and Computing; Vol. 745). Springer Verlag. DOI: 10.1007/978-3-319-77703-0_106Our work addresses the factors that influence the adoption of business analytics and intelligence (BAI) among firms. Grounded on some of the most prominent adoption models for technological innovations, we developed a conceptual model especially suited for BAI. Based on this we propose an instrument in which relevant hypotheses will be derived and tested by means of statistical analysis. We hope that the findings derived from our analysis may offer important insights for practitioners and researchers regarding the drivers that lead to BAI adoption in firms. Although other studies have already focused on the adoption of technological innovations by firms, research on BAI is scarce, hence the relevancy of our research.authorsversionpublishe

Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis

First Online: 06 October 2012Identification of predictors of cognitive trajectories through the establishment of composite or single-parameter dimensional categories of cognition and mood may facilitate development of strategies to improve quality of life in the elderly. Participants (n = 487, aged 50+ years) were representative of the Portuguese population in terms of age, gender, and educational status. Cognitive and mood profiles were established using a battery of neurocognitive and psychological tests. Data were subjected to principal component analysis to identify core dimensions of cognition and mood, encompassing multiple test variables. Dimensions were correlated with age and with respect to gender, education, and occupational status. Cluster analysis was applied to isolate distinct patterns of cognitive performance and binary logistic regression models to explore interrelationships between aging, cognition, mood, and socio-demographic characteristics. Four main dimensions were identified: memory, executive function, global cognitive status, and mood. Based on these, strong and weak cognitive performers were distinguishable. Cluster analysis revealed further distinction within these two main categories into very good, good, poor, and very poor performers. Mood was the principal factor contributing to the separation between very good and good, as well as poor and very poor, performers. Clustering was also influenced by gender and education, albeit to a lesser extent; notably, however, female gender × lower educational background predicted significantly poorer cognitive performance with increasing age. Mood has a significant impact on the rate of cognitive decline in the elderly. Gender and educational level are early determinants of cognitive performance in later life.This work was funded by the European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772). NCS is supported by a SwitchBox post-doctoral fellowship. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation