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Magnetosomes have emerged as a model system to study prokaryotic organelles and a source of biocompatible magnetic nanoparticles for various biomedical applications. However, the lack of knowledge about the transcriptional organization of magnetosome gene clusters has severely impeded the engineering, manipulation, and transfer of this highly complex biosynthetic pathway into other organisms.

Abstract Background Over the last decade Russia has introduced various policy measures to reduce alcohol consumption and alcohol-related harm at the population level. Several of these policies, such as higher pricing and taxation or restrictions of availability, may not work in the case of unrecorded alcohol consumption; they may encourage consumers to switch to unrecorded alcohol and even increase consumption. In the present qualitative interview study we explore the perception of the recently implemented alcohol policies by patients diagnosed with alcohol dependence in two Russian cities in the years 2013–2014 and shed light on possible entry-points to prevention. Methods Semi-structured in-depth expert interviews were conducted with 25 patients of state-run drug and alcohol treatment centers in two Russian cities in 2013 and 2014. The interviews were analyzed using thematic content analysis. Results All of the interviewed participants have consumed unrecorded at some point with the majority being regular consumers, mostly switching between recorded and unrecorded alcohol depending on the situation, as predominantly defined by available money and available sources of alcohol. Low price and high availability were reported as the main reasons for unrecorded consumption. Participants voiced a general mistrust of the recently implemented alcohol regulations and viewed them largely as ineffective. They expressed particular concerns over price increases and restriction of night sales of alcoholic beverages. Substantial shifts within the unrecorded alcohol market were reported, with a decreasing availability of home-made beverages in favor of alcohol surrogates in the form of non-beverage alcohol, medicinal and cosmetic compounds. At the same time consumption of home-made alcoholic beverages was seen as a strategy to avoid counterfeit alcohol, which was frequently reported for retail sale. Conclusions Despite the alcohol policy changes in the last years in Russia, consumption of unrecorded alcohol remained common for people with alcohol dependence. Reduction of availability of unrecorded alcohol, first and foremost in the form of cheap surrogates, is urgently needed to reduce alcohol-related harm. Implementation of screening and brief interventions for excessive alcohol consumption in various contexts such as primary healthcare settings, trauma treatment services or the workplace could be another important measure targeting consumers of unrecorded alcohol.

Abstract Background IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment. Methods NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics. Results The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients. Conclusion It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.

Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins affects Salmonella pathogenesis. Here we leveraged a candidate cellular GWAS screen to identify natural genetic variation in the ARHGEF26 (Rho Guanine Nucleotide Exchange Factor 26) gene that renders lymphoblastoid cells susceptible to Salmonella Typhi and Typhimurium invasion. Experimental follow-up redefined ARHGEF26's role in Salmonella epithelial cell infection. Specifically, we identified complex serovar-by-host interactions whereby ARHGEF26 stimulation of S. Typhi and S. Typhimurium invasion into host cells varied in magnitude and effector-dependence based on host cell type. While ARHGEF26 regulated SopB- and SopE-mediated S. Typhi (but not S. Typhimurium) infection of HeLa cells, the largest effect of ARHGEF26 was observed with S. Typhimurium in polarized MDCK cells through a SopB- and SopE2-independent mechanism. In both cell types, knockdown of the ARHGEF26-associated protein DLG1 resulted in a similar phenotype and serovar specificity. Importantly, we show that ARHGEF26 plays a critical role in S. Typhimurium pathogenesis by contributing to bacterial burden in the enteric fever murine model, as well as inflammation in the colitis infection model. In the enteric fever model, SopB and SopE2 are required for the effects of Arhgef26 deletion on bacterial burden, and the impact of sopB and sopE2 deletion in turn required ARHGEF26. In contrast, SopB and SopE2 were not required for the impacts of Arhgef26 deletion on colitis. A role for ARHGEF26 on inflammation was also seen in cells, as knockdown reduced IL-8 production in HeLa cells. Together, these data reveal pleiotropic roles for ARHGEF26 during infection and highlight that many of the interactions that occur during infection that are thought to be well understood likely have underappreciated complexity.

Abstract Introduction Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD‐MCI) compared to Parkinson's disease (PD‐MCI) are rare. Methods Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. Results Patients with AD‐MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD‐MCI showed lower standardized scores in a set‐shifting measure as an executive task. A cross‐validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD‐MCI versus PD‐MCI. Discussion The applied test battery successfully discriminated between AD‐MCI and PD‐MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.

Background: Meta-analyses suggest an increased prevalence of paternal depression during the perinatal period of around 10%. The relationship between paternal and maternal symptoms, however, has received little attention.Objective: To determine pooled estimates pertaining to the relationship between paternal and maternal depression during the perinatal period according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Data sources: Studies reporting on the relationship between depression in fathers and mothers between the first trimester and the first year following childbirth were identified using PubMed, PsycINFO, and EMBASE for the period between November 2009 and February 2020.Study selection: A total of 28 primary, empirical studies published in English or German, reporting effect estimates for the relationship of depression in mother–father/partner dyads, involving 11,593 couples, were included. Ten studies included multiple assessments, resulting in 64 extracted effects.Analysis: Information on correlations and odds ratios were extracted. Four random-effects analyses were conducted for the pooled association between paternal and maternal depression: (a) during the prenatal and (b) during the postnatal period, as well as for the prospective relationships between (c) paternal depression and maternal depression at a later timepoint, and (d) vice versa. Models were specified as restricted maximum-likelihood estimation. Heterogeneity was assessed using H2 and I2. Funnel plots, the Egger method, and the trim-and-fill test were used to assess publication bias. Sensitivity analyses with and without studies for which we approximated r were conducted.Data synthesis: With substantial heterogeneity, positive associations were found between paternal and maternal depression (a) during pregnancy (r = 0.238), (b) in the postnatal period (r = 0.279), as well as for the prospective relationship between (c) paternal and later maternal depression (r = 0.192), and (d) maternal and later paternal depression (r = 0.208).Conclusion: Paternal depression showed positive correlations with maternal depression across the perinatal period. Given notable methodological and cultural heterogeneity and limitations of individual studies, it was not possible to further identify determining or moderating factors. Increasing evidence for implications of parental depression for child development warrants further scientific attention.

Abstract Background Globally, illness and life expectancy follow a social gradient that puts people of lower socioeconomic status (SES) at higher risk of dying prematurely. Alcohol consumption has been shown to be a factor contributing to socioeconomic differences in mortality. However, little evidence is available from low- and middle-income countries. The objective of this study was to quantify mortality attributable to alcohol consumption in the adult (15+ years) general population of South Africa in 2015 by SES, age, and sex. Methods A comparative risk assessment was performed using individual and aggregate data from South Africa and risk relations reported in the literature. Alcohol-attributable fractions (AAFs) and alcohol-attributable mortality rates were estimated for cause-specific mortality by SES, sex, and age. Monte Carlo simulation techniques were used to calculate 95% uncertainty intervals (UI). Results Overall, approximately 62,300 (95% UI 27,000–103,000) adults died from alcohol-attributable causes in South Africa in 2015, with 60% of deaths occurring in people in the low and 15% in the high SES groups. Age-standardized, alcohol-attributable mortality rates per 100,000 adults were highest for the low SES group (727 deaths, 95% UI 354–1208 deaths) followed by the middle (377 deaths, 95% UI 165–687 deaths) and high SES groups (163 deaths, 95% UI 71–289 deaths). The socioeconomic differences were highest for mortality from infectious diseases. People of low SES had a lower prevalence of current alcohol use but heavier drinking patterns among current drinkers. Among men, AAFs were elevated at low and middle SES, particularly for the middle and higher age groups (35+). Among women, AAFs differed less across SES groups and, in the youngest age group (15–34), women of high SES had elevated AAFs. Conclusions Alcohol use contributed to vast socioeconomic differences in mortality. Where observed, elevated AAFs for people of low and middle SES arose from higher levels of consumption among current drinkers and not from the prevalence of current alcohol use per se. The findings can direct preventive measures and interventions on those at highest risk. Future research is needed to investigate socioeconomic differences in the risk functions relating alcohol use to cause-specific mortality.

Direct comparison of building energy performance levels between countries is usually not possible due to differences in climatic conditions, calculation methods, primary energy (PE) factors and input data. The aim of this paper is to analyse the differences in nearly zero energy office buildings requirements and energy calculation methodology in Denmark, Finland, and Estonia. The study is based on a newly built Estonian office building, designed to meet national NZEB requirements. To account for the climatic differences between the countries a heating-degree-days-based correction factor was applied for building envelope thermal transmittance. NZEB requirements for each country are compared with European Commission (EC) recommended values (EU 2016/1318) using normalization and benchmarking through detailed computer simulations. National NZEB primary energy threshold was needed to be reduced by 7% in Denmark and by 23% in Estonia to meet EC recommendations. At the same time, the flagship reference building, that was better than Estonian NZEB, met both Nordic and Oceanic EC recommendations. Finnish NZEB requirement was not exceeded with any building configuration applied in this study, indicating that Finnish NZEB is considerably less strict compared to Danish and Estonian ones.

Abstract Background The human pathogen Corynebacterium diphtheriae is the causative agent of diphtheria. In the 1990s a large diphtheria outbreak in Eastern Europe was caused by the strain C. diphtheriae NCTC 13129. Although the genome was sequenced more than a decade ago, not much is known about its transcriptome. Our aim was to use transcriptome sequencing (RNA-Seq) to close this knowledge gap and gain insights into the transcriptional landscape of a C. diphtheriae tox+ strain. Results We applied two different RNA-Seq techniques, one to retrieve 5′-ends of primary transcripts and the other to characterize the whole transcriptional landscape in order to gain insights into various features of the C. diphtheriae NCTC 13129 transcriptome. By examining the data we identified 1656 transcription start sites (TSS), of which 1202 were assigned to genes and 454 to putative novel transcripts. By using the TSS data promoter regions recognized by the housekeeping sigma factor σA and its motifs were analyzed in detail, revealing a well conserved −10 but an only weakly conserved −35 motif, respectively. Furthermore, with the TSS data 5’-UTR lengths were explored. The observed 5’-UTRs range from zero length (leaderless transcripts), which make up 20% of all genes, up to over 450 nt long leaders, which may harbor regulatory functions. The C. diphtheriae transcriptome consists of 471 operons which are further divided into 167 sub-operon structures. In a differential expression analysis approach, we discovered that genetic disruption of the iron-sensing transcription regulator DtxR, which controls expression of diphtheria toxin (DT), causes a strong influence on general gene expression. Nearly 15% of the genome is differentially transcribed, indicating that DtxR might have other regulatory functions in addition to regulation of iron metabolism and DT. Furthermore, our findings shed light on the transcriptional landscape of the DT encoding gene tox and present evidence for two tox antisense RNAs, which point to a new way of transcriptional regulation of toxin production. Conclusions This study presents extensive insights into the transcriptome of C. diphtheriae and provides a basis for future studies regarding gene characterization, transcriptional regulatory networks, and regulation of the tox gene in particular.

The use of wood and timber products in the construction of buildings is repeatedly pointed towards as a mean for lowering the environmental footprint. With several countries preparing regulation for life cycle assessment of buildings, practitioners from industry will presumably look to the pool of data on wood products found in environmental product declarations (EPDs). However, the EPDs may vary broadly in terms of reporting and results. This study provides a comprehensive review of 81 third-party verified EN 15804 EPDs of cross laminated timber (CLT), glulam, laminated veneer lumber (LVL) and timber. The 81 EPDs represent 86 different products and 152 different product scenarios. The EPDs mainly represent European production, but also North America and Australia/New Zealand productions are represented. Reported global warming potential (GWP) from the EPDs vary within each of the investigated product categories, due to density of the products and the end-of-life scenarios applied. Median results per kg of product, excluding the biogenic CO2, are found at 0.26, 0.24, and 0.17 kg CO2e for CLT, glulam, and timber, respectively. Results further showed that the correlation between GWP and other impact categories is limited. Analysis of the inherent data uncertainty showed to add up to ±41% to reported impacts when assessed with an uncertainty method from the literature. However, in some of the average EPDs, even larger uncertainties of up to 90% for GWP are reported. Life cycle assessment practitioners can use the median values from this study as generic data in their assessments of buildings. To make the EPDs easier to use for practitioners, a more detailed coordination between EPD programs and their product category rules is recommended, as well as digitalization of EPD data.

Abstract Background This study describes the study approach and field procedures of the MentDis_ICF65+ study, which aims to assess the prevalence of mental disorders in older adults. Methods An age-appropriate version of the Composite International Diagnostic Interview (CIDI65+) was developed and tested with regard to its feasibility and psychometric properties in a pre-test and pilot phase. In the cross-sectional survey an age-stratified, random sample of older adults (65–84 years) living in selected catchment areas of five European countries and Israel was recruited. Results N = 3142 participants (mean age 73.7 years, 50.7% female) took part in face-to-face interviews. The mean response rate was 20% and varied significantly between centres, age and gender groups. Sociodemographic differences between the study centres appeared for the place of birth, number of grandchildren, close significants, retirement and self-rated financial situation. The comparison of the MentDis_ICF65+ sample with the catchment area and country population of the study centres revealed significant differences, although most of these were numerically small. Conclusions The study will generate new information on the prevalence of common mental disorders among older adults across Europe using an age-appropriate, standardized diagnostic instrument and a harmonized approach to sampling. Generalizability of the findings and a potentially limited representativeness are discussed.