Conservation through biocultural heritage-Examples from sub-Saharan Africa

In this paper, we review the potential of biocultural heritage in biodiversity protection and agricultural innovation in sub-Saharan Africa. We begin by defining the concept of biocultural heritage into four interlinked elements that are revealed through integrated landscape analysis. This concerns the transdisciplinary methods whereby biocultural heritage must be explored, and here we emphasise that reconstructing landscape histories and documenting local heritage values needs to be an integral part of the process. Ecosystem memories relate to the structuring of landscape heterogeneity through such activities as agroforestry and fire management. The positive linkages between living practices, biodiversity and soil nutrients examined here are demonstrative of the concept of ecosystem memories. Landscape memories refer to built or enhanced landscapes linked to specific land-use systems and property rights. Place memories signify practices of protection or use related to a specific place. Customary protection of burial sites and/or abandoned settlements, for example, is a common occurrence across Africa with beneficial outcomes for biodiversity and forest protection. Finally, we discuss stewardship and change. Building on local traditions, inclusivity and equity are essential to promoting the continuation and innovation of practices crucial for local sustainability and biodiversity protection, and also offer new avenues for collaboration in landscape management and conservation.European Commission Marie Curie ITN Swedish Research Council Sid

An epigenetic clock for human skeletal muscle.

BACKGROUND: Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan-tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue. METHODS: To address this, we developed a more accurate, muscle-specific epigenetic clock based on the genome-wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18-89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome-wide association study of age-associated DNA methylation patterns in skeletal muscle. RESULTS: The newly developed clock uses 200 cytosine-phosphate-guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine-phosphate-guanine dinucleotides of the pan-tissue clock. The muscle clock outperformed the pan-tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan-tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs. ρ = 0.51 for the pan-tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies. CONCLUSIONS: We have developed a muscle-specific epigenetic clock that predicts age with better accuracy than the pan-tissue clock. We implemented the muscle clock in an r package called Muscle Epigenetic Age Test available on Bioconductor to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle-specific biological ageing processes

Work-related psychosocial events as triggers of sick leave - results from a Swedish case-crossover study

<p>Abstract</p> <p>Background</p> <p>Although illness is an important cause of sick leave, it has also been suggested that non-medical risk factors may influence this association. If such factors impact on the period of decision making, they should be considered as triggers. Yet, there is no empirical support available.</p> <p>The aim was to investigate whether recent exposure to work-related psychosocial events can trigger the decision to report sick when ill.</p> <p>Methods</p> <p>A case-crossover design was applied to 546 sick-leave spells, extracted from a Swedish cohort of 1 430 employees with a 3-12 month follow-up of new sick-leave spells. Exposure in a case period corresponding to an induction period of one or two days was compared with exposure during control periods sampled from workdays during a two-week period prior to sick leave for the same individual. This was done according to the matched-pair interval and the usual frequency approaches. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).</p> <p>Results</p> <p>Most sick-leave spells happened in relation to acute, minor illnesses that substantially reduced work ability. The risk of taking sick leave was increased when individuals had recently been exposed to problems in their relationship with a superior (OR 3.63; CI 1.44-9.14) or colleagues (OR 4.68; CI 1.43-15.29). Individuals were also more inclined to report sick on days when they expected a very stressful work situation than on a day when they were not under such stress (OR 2.27; CI 1.40-3.70).</p> <p>Conclusions</p> <p>Exposure to problems in workplace relationships or a stressful work situation seems to be able to trigger reporting sick. Psychosocial work-environmental factors appear to have a short-term effect on individuals when deciding to report sick.</p

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening

The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti

In many taxa, sex chromosomes are heteromorphic and largely non-recombining. Evolutionary models predict that spread of recombination suppression on the Y chromosome is fueled by the accumulation of sexually antagonistic alleles in close linkage to the sex determination region. However, empirical evidence for the existence of sexually antagonistic alleles is scarce. In the mosquito Aedes aegypti, the sex-determining chromosomes are homomorphic. The region of suppressed recombination, which surrounds the male-specific sex-determining gene, remains very small, despite ancient origin of the sex chromosomes in the Aedes lineage. We conducted a genetic analysis of the A. aegypti chromosome region tightly linked to the sex locus. We used a strain with an enhanced green fluorescent protein (EGFP)-tagged transgene inserted near the male-determining gene to monitor crossing-over events close to the boundary of the sex-determining region (SDR), and to trace the inheritance pattern of the transgene in relation to sex. In a series of crossing experiments involving individuals with a recombinant sex chromosome we found developmental abnormalities leading to 1:2 sex biases, caused by lethality of half of the male or female progeny. Our results suggest that various factors causing sex-specific lethal effects are clustered within the neighborhood of the SDR, which in the affected sex are likely lost or gained through recombination, leading to death. These may include genes that are recessive lethal, vital for development and/or sexually antagonistic. The sex chromosome fragment in question represents a fascinating test case for the analysis of processes that shape stable boundaries of a non-recombining region

Attenuation of Helicobacter pylori-induced gastric inflammation by prior cag− strain (AM1) infection in C57BL/6 mice

Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag+ strain (SS1) and cag− strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa. Results: Mice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1β and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/ SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3+ T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-β were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues. Conclusions: These data suggested that prior H. pylori cag− strain infection attenuated the severity of gastric pathology induced by subsequent cag+ strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent H. pylori strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expressio

Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins

Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 −156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19–5.87; p = 0.017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p = 0.0009). In HUVECs, atorvastatin dose-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response

Multiple Novel Nesprin-1 and Nesprin-2 Variants Act as Versatile Tissue-Specific Intracellular Scaffolds

<div><h3>Background</h3><p>Nesprins (<u>N</u>uclear <u>e</u>nvelope <u>s</u>pectrin-<u>r</u>epeat <u>p</u>roteins) are a novel family of giant spectrin-repeat containing proteins. The nesprin-1 and nesprin-2 genes consist of 146 and 116 exons which encode proteins of ∼1mDa and ∼800 kDa is size respectively when all the exons are utilised in translation. However emerging data suggests that the nesprins have multiple alternative start and termination sites throughout their genes allowing the generation of smaller isoforms.</p> <h3>Results</h3><p>In this study we set out to identify novel alternatively transcribed nesprin variants by screening the EST database and by using RACE analysis to identify cDNA ends. These two methods provided potential hits for alternative start and termination sites that were validated by PCR and DNA sequencing. We show that these alternative sites are not only expressed in a tissue specific manner but by combining different sites together it is possible to create a wide array of nesprin variants. By cloning and expressing small novel nesprin variants into human fibroblasts and U2OS cells we show localization to actin stress-fibres, focal adhesions, microtubules, the nucleolus, nuclear matrix and the nuclear envelope (NE). Furthermore we show that the sub-cellular localization of individual nesprin variants can vary depending on the cell type, suggesting any single nesprin variant may have different functions in different cell types.</p> <h3>Conclusions</h3><p>These studies suggest nesprins act as highly versatile tissue specific intracellular protein scaffolds and identify potential novel functions for nesprins beyond cytoplasmic-nuclear coupling. These alternate functions may also account for the diverse range of disease phenotypes observed when these genes are mutated.</p> </div