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We review some of the current insights derived from the analyses of new large-scale, genome-wide autosomal variation data studies incorporating Ethiopians. Consistent with their substantial degree of cultural and linguistic diversity, genetic diversity among Ethiopians is higher than that seen across much larger geographic regions worldwide. This genetic variation is associated in part with ethnic identity, geography and linguistic classification. Numerous and varied admixture events have been inferred in Ethiopian groups, for example, involving sources related to present-day groups in West Eurasia and North Africa, with inferred dates spanning a few hundred to more than 4500 years ago. These disparate inferred ancestry patterns are correlated in part with groups’ broad linguistic classifications, though with some notable exceptions. While deciphering these complex genetic signals remains challenging with available data, these studies and other projects focused on resolving competing hypotheses on the origins of specific ethnolinguistic groups demonstrate how genetic analyses can complement findings from anthropological and linguistic studies on Ethiopians.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

The rich linguistic, ethnic and cultural diversity of Ethiopia provides an unprecedented opportunity to understand the level to which cultural factors correlate with–and shape–genetic structure in human populations. Using primarily new genetic variation data covering 1,214 Ethiopians representing 68 different ethnic groups, together with information on individuals’ birthplaces, linguistic/religious practices and 31 cultural practices, we disentangle the effects of geographic distance, elevation, and social factors on the genetic structure of Ethiopians today. We provide evidence of associations between social behaviours and genetic differences among present-day peoples. We show that genetic similarity is broadly associated with linguistic affiliation, but also identify pronounced genetic similarity among groups from disparate language classifications that may in part be attributable to recent intermixing. We also illustrate how groups reporting the same culture traits are more genetically similar on average and show evidence of recent intermixing, suggesting that shared cultural traits may promote admixture. In addition to providing insights into the genetic structure and history of Ethiopia, we identify the most important cultural and geographic predictors of genetic differentiation and provide a resource for designing sampling protocols for future genetic studies involving Ethiopians., Ethiopia is one of the most ethnically and culturally diverse countries. Here, the authors look at genetic and cultural variation in 1,214 Ethiopians to unravel the relationship between genetic admixture and cultural factors.

Few jobs come without irritations, and foreign language instruction comes with its own particular set of frustrations which, when accumulated, can lead to stress and eventual burnout for teachers. One mechanism for reducing such frustrations is that of emotion regulation, the cognitive and behavioral strategies individuals employ to manage the emotions they experience or display. To date, no known studies have reported specifically on the in-class frustration experienced by language teachers, or on how teachers regulate their feelings of frustration. Herein, the authors discuss the experiences of seven EFL teachers at a university in Japan obtained through a series of semistructured interviews, classroom observations and corresponding stimulated-recall sessions. The authors discuss four salient thematic frustrations: student apathy, classroom silence, misbehavior in the context of relational strain, and working conditions. The results reveal that participants applied contextually-dependent emotion regulation behaviors, the success of which was often contingent on the participants’ levels of confidence and control over the stressors. Thus, participants showed more success in managing pervasive low-level stressors such as apathy and silence, and more support would be welcome to aid them to manage more debilitating stressors such as student misbehavior. The authors offer suggestions for teachers, trainers and institutions on reducing frustration.

Teachers and advisors involved in the emotional business of language education feel frustrated from time to time, and if such emotions are not managed healthily, they may lead to negative outcomes such as stress and burnout. One important system for taking control of frustration is emotion regulation, the cognitive and behavioural strategies through which individuals manage their emotions. In this short article, I define frustration and discuss its negative impact on the language classroom. I then introduce a structured reflective journaling tool, built upon Gross’s Process model of emotion regulation (Gross, 2014, 2015) which may help teachers and advisors develop greater awareness and control over experiences of frustration.

Broadening participation in computing education for K-12 students requires all levels of the education system to collaborate on five critical needs: 1) creating diverse student opportunities and access to CS activities; 2) empowering highly qualified, highly skilled CS teachers; 3) developing relevant and accessible CS courses and curricula; 4) establishing CS policy and leadership at the local and state levels; and 5) engaging communities and industry partners in broadening participation in CS.

The reuse of nests by the same or different species can save a colony energy and resources. Furthermore, it can increase colony growth and the production of brood. The queenless ant Dinoponera quadriceps builds deep nests in Caatinga to escape from the dry and hot environment. The reuse of deep nests from other species can provide D. quadriceps with protection from high temperature, whilst saving on the energy required to build new nests. Here, we present the first finding of D. quadriceps reusing the nest of Atta sexdens species.

Rationale: B cells contribute to atherosclerosis through subset specific mechanisms. Whereas some controversy exists about the role of B-2 B cells, B-1a B cells are atheroprotective. The function of B-1b B cells, a unique subset of B-1 cells that can produce T cell-independent (TI) memory, has not been studied within the context of atherosclerosis. Objective: To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet induced atherosclerosis. Methods and Results: We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation specific epitopes (OSE) on LDL in vitro in response to activating stimulation. Additionally, we demonstrate that B-1b cells provide direct atheroprotection after adoptive transfer into B and T cell deficient (Rag1-/-Apoe-/-) hosts. To support these findings, we utilize a B cell specific Id3 knockout mouse model (Id3BKO), which develops increased numbers of B-1b cells systemically, to demonstrate that these mice develop attenuated atherosclerosis and increased OSE IgM antibodies compared to wild-type controls (Id3WT) after being fed a Western diet for 16 weeks. Finally, we report that the presence of a functionally relevant homozygous SNP in ID3 in humans associates with increased proportion of circulating B-1 cells and anti-MDA-LDL IgM and that the percentage of circulating B-1 cells is directly associated with the amount of anti-MDA-LDL IgM suggesting clinical relevance. Conclusions: These results provide novel evidence that B-1b B cells produce atheroprotective OSE IgM antibodies and protect against atherosclerosis in mice, and suggest that similar mechanisms may occur in humans.

Background Participation of renal cells in the pathogenesis of staphylococcal enterotoxin B (SEB) is critical for late cleansing and sequestration of the antigens facilitated by CD1d mediated antigen sensing and recognition. This is a noted deviation from the typical antigen recognition process that recruits the major histocompatibility complex class II (MHC II) molecules. The immunological importance of CD1d is underscored by its influences on the performances of natural killer T-cells and thereby mediates the innate and adaptive immune systems. Results Using diffraction-based dotReady™ immunoassays, the present study showed that SEB directly and specifically conjugated to CD1d. The specificity of the conjugation between SEB and CD1d expressed on human renal proximal tubule epithelial cells (RPTEC) was further established by selective inhibition of CD1d prior to its exposure to SEB. We found that SEB induced the expression of CD1d on the cell surface prompting a rapid conjugation between them. The mRNA transcripts encoding CD1d remained elevated potentially after completing the antigen cleansing process. Conclusion Molecular targets associated with the delayed pathogenic response have essential therapeutic values. Particularly in the event of bioterrorism, the caregivers are typically able to intervene much later than the toxic exposures. Given circumstances mandate a paradigm shift from the conventional therapeutic strategy that counts on targeting the host markers responding to the early assault of pathogens. We demonstrated the role of CD1d in the late stage of pathogen recognition and cleansing, and thereby underscored its clinical potential in treating bioweaponizable antigens, such as Staphylococcal enterotoxin B (SEB). Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0344-5) contains supplementary material, which is available to authorized users.

Introduction: B cells have been shown to have subset specific functions in atherosclerosis. B1a B cells, which contribute to innate immunity, are atheroprotective due to the spontaneous generation of protective natural antibodies. B1b B cells, the sister population to B1a B cells, also produce natural antibodies and unlike B1a B cells, have memory and inducible properties. B1b B cells have not been studied in atherosclerosis. Our lab has demonstrated that the helix-loop-helix transcription factor Id3 is important for B cell mediated atheroprotection. However, how Id3 in B cells regulates atheroprotection is incompletely understood. Hypothesis: Loss of Id3 specifically in B cells regulates an atheroprotective subset. Methods: To determine the impact of loss of Id3 specifically in B cells, we generated B cell specific Id3 knockout mice on the Apoe -/- background (Id3 fl/fl Apoe -/- CD19 cre/+ ). To measure atherosclerosis, 8 week old male Id3 fl/fl Apoe -/- CD19 cre/+ mice were fed Western diet for 16 weeks (n=7). These mice developed significantly less atherosclerosis in the aortic sinus compared to litter matched wildtype controls (Id3 fl/fl Apoe -/- CD19 +/+ , n=10) suggesting loss of Id3 in B cells was atheroprotective. Additionally, immunohistochemistry of atherosclerotic plaques demonstrated decreased intraplaque macrophage accumulation and fewer apoptotic bodies compared to wildtype. Immunophenotyping of Id3 fl/fl Apoe -/- CD19 cre/+ mice by flow cytometry revealed a specific increase of B1b B cells in the peritoneal cavity, spleen, and in circulation compared to wildtype (n=12-19). Additionally, 8 week old Id3 fl/fl Apoe -/- CD19 cre/+ mice (n=8) were shown by ELISA to have significantly greater circulating IgM and, after 16 weeks of Western diet feeding (n=10), significantly greater circulating natural antibodies compared to wildtype (n= 9 & 11 respectively). Conclusion: B cell-specific loss of Id3 enhances the B1b B cell pool, natural antibody production, and atheroprotection suggesting B1b B cells are important in defending against atherosclerosis in an antibody dependent manner.

Background Aortic homing of B cells and B cell mediated atheroprotection depend on the helix-loop-helix (HLH) transcription factor Id3. We identified that CCR6, a downstream target of Id3, is also essential for B cell homing to the aorta. Id3 functions through dominant negative inhibition of basic-HLH transcription factors such as E proteins. We have shown that a non-synonomous single nucleotide polymorphism in Id3 correlates with human carotid intimal medial thickness (cIMT). The protein encoded by this risk allele shows attenuated interaction with E12 yet whether this property is shared with other E proteins and the potential impact of Id3 and E12 on CCR6 expression in B cell subsets is unknown. Results Co-IPs of ancestral and polymorphic Id3 with the four known E proteins showed that E12, and not other E proteins, had significantly decreased interaction with polymorphic Id3. To address the regulatory role of Id3 on CCR6 in B cells, B cell subsetting by flow cytometry was done showing that B cell specific Id3 knockout mice (Id3fl/flApoe-/-CD19cre/+) indeed have significantly fewer CCR6 positive B cells which is in agreement with our previous findings in global Id3 knockout mice. To address the regulatory role of E12 on CCR6 expression similar subsetting of global E12 knockout mice (E12-/-Apoe-/-) was done showing they have significantly more CCR6 positive B cells of all subsets (B1a, B1b, B2) compared to wildtype. In particular the atheroprotective B1a subset had the greatest percentage increase due to loss of E12 compared to other subsets. Finally, we addressed whether CCR6 on human B cells correlates with human atherosclerosis. We found that coronary plaque burden and stenosis as measured by intravascular ultrasound (IVUS) in patients undergoing coronary catheterization correlated inversely with the average amount of CCR6 on B cells. Conclusions Our data suggests that Id3 is a key activator of CCR6 expression in B cells through dominant negative inhibition of E12. Furthermore, it raises the interesting possibility that CCR6 could play an important atheroprotective role through its regulation of B cell homing in humans.

The Tup1-Cyc8 (Ssn6) complex is a well characterized and conserved general transcriptional repressor complex in eukaryotic cells. Here, we report the identification of the Tup1 (TupA) homolog in the filamentous fungus Aspergillus niger in a genetic screen for mutants with a constitutive expression of the agsA gene. The agsA gene encodes a putative alpha-glucan synthase, which is induced in response to cell wall stress in A. niger. Apart from the constitutive expression of agsA, the selected mutant was also found to produce an unknown pigment at high temperatures. Complementation analysis with a genomic library showed that the tupA gene could complement the phenotypes of the mutant. Screening of a collection of 240 mutants with constitutive expression of agsA identified sixteen additional pigment-secreting mutants, which were all mutated in the tupA gene. The phenotypes of the tupA mutants were very similar to the phenotypes of a tupA deletion strain. Further analysis of the tupA-17 mutant and the DeltatupA mutant revealed that TupA is also required for normal growth and morphogenesis. The production of the pigment at 37 degrees C is nitrogen source-dependent and repressed by ammonium. Genome-wide expression analysis of the tupA mutant during exponential growth revealed derepression of a large group of diverse genes, including genes related to development and cell wall biosynthesis, and also protease-encoding genes that are normally repressed by ammonium. Comparison of the transcriptome of up-regulated genes in the tupA mutant showed limited overlap with the transcriptome of caspofungin-induced cell wall stress-related genes, suggesting that TupA is not a general suppressor of cell wall stress-induced genes. We propose that TupA is an important repressor of genes related to development and nitrogen metabolism.

This paper considers several broad issues in the context of probabilistic assessment of the benefits of curtailing mercury (Hg) emissions from U.S. coal-fired power plants, based on information developed from recent literature and epidemiology studies of health effects of methylmercury. Exposure of the U.S. population is considered on the national scale, in large part because of recent questions arising from survey and experimental data about the relative importance of local deposition of airborne Hg. Although epidemiological studies have provided useful information, safe levels of Hg exposure remain uncertain, in part because of other dietary considerations in the populations that were studied. For example, much of the seafood consumed in one of the major studies was also contaminated with polychlorinated biphenyls, as are fish taken from some U.S. fresh waters. The primary epidemiological approach involves cross-study comparisons in relation to mean exposures, rather than detailed critiques of individual effects reported in each study. U.S. exposures are seen to be well below the levels at which adverse health effects are reported. This analysis supports the conclusion that unilateral reduction of Hg emissions from U.S. coal-fired power plants alone is unlikely to realize significant public health benefits.

Prothrombin is a single-chain protein ( M r 72,000) which can be converted to the two-chain coagulation enzyme thrombin ( M r 37,000) by a protein present in the venom of Echis carinatus . During the course of this reaction, several intermediates and products are produced. We have found that size-exclusion high-performance liquid chromatography is a useful method for identifying the various intermediates as well as for determining the rates at which they are produced. The intermediates were identified by comparison with either authentic proteins or sodium dodecyl sulfate-polyacrylamide gel electrophoresis of duplicate samples. The separation of prothrombin, thrombin, and the other products was accomplished in less than 18 min using a TSK Type SW 3000 column equilibrated with 0.1 m Tris buffer, pH 7.2, containing 0.15 m NaCl. Estimates of the molecular weights of the products determined from calibration curves did not necessarily agree with actual values. Meizothrombin, the two-chain active form of prothrombin, has a longer elution time than prothrombin, although both molecules have the same molecular weight. Ca(II) increased the elution time of prothrombin and Fragment 1. The rate of disappearance of prothrombin as determined by peak-height analysis agreed with the rate of formation of active enzyme as determined by active site titration. Thus, high-performance liquid chromatography is a rapid analytical tool for the study of the proteolytic modification of proteins.

The thrombin specific chromogenic substrates, Phe-Pipecolyl-Arg-p-nitroanilide (S-2238) and benzoyl-Phe-Val-Arg-p-nitroanilide (S-2160) are inhibitors of factor Xa amidolytic and proteolytic activity. The inhibition is of the partial noncompetitive type in that no change in the Km for the hydrolyzed substrate was observed and some factor Xa activity remains even at infinite inhibitor concentration. High performance liquid chromatographic analysis indicated that the inhibitors were essentially free of either p-nitroaniline or free peptide contamination. Neither p-nitroaniline nor acid hydrolyzed inhibitors were capable of inhibiting factor Xa demonstrating that a minimal peptide structure is necessary for inhibition. Our results indicate that factor Xa contains a regulatory site which, when occupied by certain peptides, causes a decrease in the rate of catalysis.

Factor X is the zymogen of the proteolytic coagulation enzyme Factor Xa. Since the activation of Factor X to Factor Xa may be a rate limiting step of the coagulation cascade we have begun investigations of the mechanism of this reaction. Human Factor X has been purified 6000-fold from human plasma and the final product is over 95% pure as judged by Polyacrylamide gel electrophoresis. Human Factor X has a monomeric molecular weight of 75,000 and consists of two chains held together by a disulphide bridge. The molecular weight of the heavy chain is 56,000 and that of the light chain is 17,500. The venom coagulant protein of V. russelli (RVV-X) activates human Factor X by cleaving the heavy chain. When fully activated, human Factor Xa shows two bands on Polyacrylamide gel electrophoresis indicating that human Factor Xa like the bovine enzyme has two molecular forms.The kinetic mechanism of the activation reaction has been investigated utilizing the chromogenic Factor Xa substrate Bz-Ile-Glu-Gly-Arg-p-Nitroanilide (S-2222). The reaction has an absolute requirement for Ca; Mg cannot substitute for Ca, however Mg can increase the Vmax of Xa formation in the presence of suboptimal concentrations of Ca. Both Ca and Mg effects exhibit positive cooperativity. Our data indicate that human Factor X has at least three cooperative metal binding sites some of which are specific for Ca.