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Ridgway F. Shinn's biography of Arthur Berriedale Keith, 1879-1944. The Chief Ornament of Scottish Learning (Aberdeen: U.P., 1990; pp. xv + 386. £25) displays many of the characteristics of his [...]

In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 GCKR, rs17496332 PRMT6, rs3779195 BAIAP2L1, rs10454142 PPP1R21, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs440837 ZBTB10, rs12150660 SHBG, and rs8023580 NR2F2 have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 PPP1R21 ([additive genetic model] OR = 1.31; 95%CI = 1.08–1.65; pperm = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 PPP1R21 (included in all nine models, 100%) and four more SNPs—rs7910927 JMJD1C (five models, 55.56%), rs17496332 PRMT6 (four models, 44.44%), rs780093 GCKR (four models, 44.44%), and rs440837 ZBTB10 (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia. [ABSTRACT FROM AUTHOR]

ERH is a 100 to about 110 aa nuclear protein with unique primary and three-dimensional structures that are very conserved from simple eukaryotes to humans, albeit some species have lost its gene, with most higher fungi being a noteworthy example. Initially, studies on Drosophila melanogaster implied its function in pyrimidine metabolism. Subsequently, research on Xenopus laevis suggested that it acts as a transcriptional repressor. Finally, studies in humans pointed to a role in pre-mRNA splicing and in mitosis but further research, also in Caenorhabditis elegans and Schizosaccharomyces pombe, demonstrated its much broader activity, namely involvement in the biogenesis of mRNA, and miRNA, piRNA and some other ncRNAs, and in repressive heterochromatin formation. ERH interacts with numerous, mostly taxon-specific proteins, like Mmi1 and Mei2 in S. pombe, PID-3/PICS-1, TOST-1 and PID-1 in C. elegans, and DGCR8, CIZ1, PDIP46/SKAR and SAFB1/2 in humans. There are, however, some common themes in this wide range of processes and partners, such as: (a) ERH homodimerizes to form a scaffold for several complexes involved in the metabolism of nucleic acids, (b) all these RNAs are RNA polymerase II transcripts, (c) pre-mRNAs, whose splicing depends on ERH, are enriched in transcripts of DNA damage response and DNA metabolism genes, and (d) heterochromatin is formed to silence unwanted transcription, e.g., from repetitive elements. Thus, it seems that ERH has been adopted for various pathways that serve to maintain genome integrity. [ABSTRACT FROM AUTHOR]

Microwave-induced oxidation and UV/TiO2 photocatalytic technologies are widely used for organic wastewater treatment. Furthermore, the combination of these technologies (MW/UV/TiO2) result in a new advanced oxidation process. As a green and efficient photocatalytic degradation technology, MW/UV/TiO2 is favored for its advantages of high removal rate, short time use, wide concentration range, low cost, good stability, and no secondary pollution. Herein, this paper has summarized insights into the removal process by unveiling the degradation mechanism of organic compounds with MW-assisted technology. Additionally, water quality factors and process parameters affect the photocatalytic efficiencies, consisting of initial concentration, initial volume, TiO2 dosage, UV intensity, microwave power, temperature, pH, and fluid velocity, which have been systematically analyzed. Finally, possible future research directions and guidelines are proposed. Our findings will provide a way forward for the development of effective microwave-assisted remediation technologies that are broadly applicable to various environmental contamination scenarios. [ABSTRACT FROM AUTHOR]

Pluripotency is a crucial feature of pluripotent stem cells, which are regulated by the core pluripotency network consisting of key transcription factors and signaling molecules. However, relatively less is known about the molecular mechanisms that modify the core pluripotency network. Here we used the CAPTURE (CRISPR Affinity Purification in situ of Regulatory Elements) to unbiasedly isolate proteins assembled on the Nanog promoter in mouse embryonic stem cells (mESCs), and then tested their functional relevance to the maintenance of mESCs and reprogramming of somatic cells. Gene ontology analysis revealed that the identified proteins, including many RNA-binding proteins (RBPs), are enriched in RNA-related functions and gene expression. ChIP-qPCR experiments confirmed that BCLAF1, FUBP1, MSH6, PARK7, PSIP1, and THRAP3 occupy the Nanog promoter region in mESCs. Knockdown experiments of these factors show that they play varying roles in self-renewal, pluripotency gene expression, and differentiation of mESCs as well as in the reprogramming of somatic cells. Our results show the utility of unbiased identification of chromatin-associated proteins on a pluripotency gene in mESCs and reveal the functional relevance of RBPs in ESC differentiation and somatic cell reprogramming. [ABSTRACT FROM AUTHOR]

How and why distinct genetic alterations, such as BRCA1 mutation, promote tumorigenesis in certain tissues, but not others, remain an important issue in cancer research. The underlying mechanisms may reveal tissue-specific therapeutic vulnerabilities. Although the roles of BRCA1, such as DNA damage repair and stalled fork stabilization, obviously contribute to tumor suppression, these ubiquitously important functions cannot explain tissue-specific tumorigenesis by BRCA1 mutations. Recent advances in our understanding of the cancer genome and fundamental cellular processes on DNA, such as transcription and DNA replication, have provided new insights regarding BRCA1-associated tumorigenesis, suggesting that G-quadruplex (G4) plays a critical role. In this review, we summarize the importance of G4 structures in mutagenesis of the cancer genome and cell type-specific gene regulation, and discuss a recently revealed molecular mechanism of G4/base excision repair (BER)-mediated transcriptional activation. The latter adequately explains the correlation between the accumulation of unresolved transcriptional regulatory G4s and multi-level genomic alterations observed in BRCA1-associated tumors. In summary, tissue-specific tumorigenesis by BRCA1 deficiency can be explained by cell type-specific levels of transcriptional regulatory G4s and the role of BRCA1 in resolving it. This mechanism would provide an integrated understanding of the initiation and development of BRCA1-associated tumors. [ABSTRACT FROM AUTHOR]

Matrin3 is a highly conserved inner nuclear matrix protein involved in multiple stages of RNA metabolism. Although Matrin3 may also play a role in DNA repair, its precise roles have remained unclear. In this study, we showed that the depletion of Matrin3 led to decreased homologous recombination (HR) efficiency and increased radiation sensitivity of cells. Matrin3-depleted cells showed impaired DNA damage-dependent focus formation of RAD51, a key protein in HR. These findings suggest that Matrin3 promotes HR by regulating RAD51. [ABSTRACT FROM AUTHOR]

Purpose – Concentrating on internal commentaries, this paper aims to consider the factors that have contributed to the resistance to the introduced reporting and accountability for the whole-of-government of Vanuatu. Design/methodology/approach – The view from the centre considers documentary evidence of the Auditor-General's commentaries on the whole of Vanuatu government reporting. Textual analysis takes into account the complexity of Vanuatu's political, social, economic, cultural and historical background, together with views from the periphery about the expectations raised about Vanuatu's constitutional accountability. Findings – In recent times, in Vanuatu, there have been no annual reports generated by the Auditor-General and, thus, no examination and audit of the accounts of the government of Vanuatu, suggesting a resistance to the introduced Condominium concepts of parliamentary accountability of the whole of Vanuatu government reporting. In the time the Auditor-General's Office (AGO) did produce reports that were largely ignored by parliament and its Public Accounts Committee (PAC). Research limitations/implications – Introduced ideas of accountability as reflected in the constitution of Vanuatu have an uncertain space. Introduced Westminster systems of government raise an expectation to uphold the intent and provisions of constitutional accountability through either Western-narrow or Western-broad government reporting. Textual analysis of the Auditor-General's commentaries show that to develop and fully leverage ideas of imported concepts, such as accountability, those on the periphery need to understand the "centre", their nature, characteristics and configuration. Practical implications – Greater funding and staffing of the AGO would assist in the examination and audit of the accounts of the government of Vanuatu. Greater interest by parliamentary oversight committees, such as the PAC, in the Auditor-General's work would help this examination and audit process. Originality/value – The originality of the paper rests in considering Vanuatu's agency's own government reporting through internal points of reference. [ABSTRACT FROM AUTHOR]

The concept of 'networks' in the British world has captivated the attention of historians in recent years, with theoretical frameworks now offered to chart the chronology of such phenomena. This article examines these frameworks critically through the lens of British world municipalities, examining the transfer of people and ideas between 1890 and 1939. It contemplates the significance of British world publications such as the Municipal Journal, appearing after 1890, in the facilitation of British world progressivism and its role in formalising networks; also the travels of municipal employees and the correspondence of town clerks in the first half of the twentieth century. Consideration is given to the place of Australian and New Zealand cities in such global networks. The article reflects on whether a move from 'ad hoc' networks before 1914 to more formal ones after 1920 is a credible way of characterising the period from the perspective of the Southern hemisphere cities. [ABSTRACT FROM AUTHOR]

Purpose - The purpose of this paper is to address the question of whether two early Australian public accounts committees were established for the purpose of legitimating governments of the time. Design/methodology/approach - The paper addressed these issues through a study of the establishment, early work and abolition in the 1930s of the Victorian Committee of Public Accounts (VCPA) and the Joint Committee of Public Accounts (JCPA). Findings - Clear evidence is found that the Joint Committee of Public Accounts (JCPA) had been copied from the VCPA and that the VCPA had been copied from the UK House of Commons Committee of Public Accounts, which was established in 1861. This would indicate that the primary objective in the establishment of both these committees was legitimation rather than control. It was found that the subsequent work of both the VCPA and the JCPA showed a drift away from an accounting focus towards a policy focus. This is similar to the JCPA experience described by Degeling et al in relation to the JCPA, which also supports the legitimation argument. It was also found that both committees could be disestablished with relative ease because their legitimating purpose was no longer strong enough to demand their continuation and that, in fact, their abolition became the factor that served a legitimating purpose for governments. Originality/value - The paper suggests that the ideas of legitimation and mimetic isomorphism provide a more convincing explanation for the nature and work of these two public accounts committees than the idea of accounting colonisation. [ABSTRACT FROM AUTHOR]

Limited research on revictimization has examined the role of social support, which is known to affect sexual assault survivors' psychological recovery. Measuring social support also provides a more ecological approach to understanding revictimization, as it assesses the possible role of those in the survivors' environment. The current study examined how social support and disclosure experiences of 625 community-based survivors related to their revictimization status over a 12-month period. Results showed differences between revictimized and nonrevictimized survivors in terms of who they disclosed to about their assault. In addition, revictimized survivors received less informational and emotional support and more blaming reactions. Implications for future research regarding using an ecological approach to better understand revictimization risk are discussed. © 2008 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The bilateral relationship between Australia and the UK has been an extremely significant relationship for Australia, albeit one that carries with it considerable historical baggage. This article offers an overview of some key issues in the bilateral relationship, with a particular focus on the years following the second world war. Underpinned by ties in defence and security, trade and investment, and a multitude of social and cultural connections, the relationship remained strong – although sometimes irritable. With the 1960s and 1970s came profound changes, affecting practically every aspect of the relationship and unravelling some fundamental Australian assumptions, including those about the Commonwealth of Nations. The article concludes by briefly examining prospects for the contemporary bilateral relationship. [ABSTRACT FROM AUTHOR]

A central element of the narrative circulated by the Tibet Movement has been that China has carried out genocide and practised colonialism in Tibet. These notions are, for the most part, uncritically accepted by politicians and the media, especially in the West. This essay challenges such characterizations as inept and as obstacles to resolving the Tibet Question. It looks at whether convincing empirical evidence of physical and cultural genocide in Tibet exists, in light of the most common understanding of such practices as rooted in efforts to destroy a people and its culture. The essay also considers what the contours of colonialism have been in light of its principal modern experience, that of European, US and Japanese colonization, and determines whether the Tibet case fits these characteristics. The essay concludes that a critique of China's policies and practices in Tibet would be best served by focusing on actual problems experienced by Tibetans. [ABSTRACT FROM AUTHOR]

It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. The sample comprised 839 girls and 741 boys from 792 intact families and 99 girls and 67 boys from 83 stepfather families from a population-based registry of twins aged between 8 and 17 years. Children's current psychiatric symptoms were assessed at personal interview with the child, mother and father. Parental histories of psychiatric disorder were assessed at personal interview with each residential parent. Associations between CD symptoms and parental alcoholism were characterized using both linear and Poisson regression, and results are presented with and without adjustment for maternal drug use during pregnancy, parental conflict, and estimated socioeconomic status (SES) based on census tract data. Mothers from stepfather families had a higher lifetime prevalence of alcoholism, antisocial personality disorder, depression and social phobia than mothers from intact families. Stepfathers had a higher lifetime prevalence of alcoholism and depression than biological fathers from intact families. Children from stepfather families had more externalizing (CD/ODD) symptoms than children from intact families. Girls who lived with an alcoholic stepfather had significantly more CD symptoms than girls who lived with an alcoholic biological father. Boys who lived with an alcoholic stepfather had significantly fewer CD symptoms than boys who lived with an alcoholic biological father. This sex difference was statistically significant. Adjustment for maternal drug use during pregnancy, parental conflict, and estimated SES based on census tract data did not change these findings. Children living in stepfather families are exposed to more parental psychiatric risk factors than children from intact families. The increased risk for CD symptoms in girls (but not boys) from stepfather families is partly mediated by or associated with the stepfather's history of alcoholism. [ABSTRACT FROM AUTHOR]

A meta-analysis was performed on 50 family, twin, and adoption studies in which problem drinking and alcohol dependence served as the primary criterion measure. The results showed that far from being an established "fact," the genetic foundations of alcohol misuse are modest and heterogeneous. A weighted mean phi effect size of 0.12 (95% Confidence Interval = 0.11-0.12) was obtained for the total sample of 72 effect sizes. Four potential moderator variables (proband gender, sample nationality, pattern severity, year of publication) were examined with outcomes confirming that the heritability of alcohol misuse is stronger in males and in studies employing more severe definitions of abuse (alcoholism, alcohol dependence). When the effect size measure was restricted to studies using male subjects with more severe diagnoses of alcohol misuse, the unweighted mean phi effect size was only 0.18 (95% Confidence Interval = 0.15-0.21), with an even smaller weighted mean phi effect size of 0.15 (95% Confidence Interval = 0.12-0.18); results which indicate an upper limit of 30-36% for the heritability of alcohol misuse. [ABSTRACT FROM AUTHOR]

The article presents a list of publications on the economic and social history of Great Britain and Ireland. Some of the publications are--"Examination Roll of Arbroath," edited by F. Davidson, "Farmworkers: A Social and Economic History: 1770-1980," by A. Armstrong, "The Diffusion of Vetches in Medieval England," by B.M.S. Campbell, "Horses in Shakespeare's England," by A. Dent, "Countryside Planning in Practice the Scottish Experience," edited by P.H. Selman, "The Growth of the London Carrying Trade: 1681-1838," by D. Gerhold, "The British Iron Industry: 1700-1850," by J.R. Harris, "Business, Banking and Politics: The Case of British Steel, 1918-1939," by S. Tolliday" and others.

Simple Summary: Paradoxically, although the steroid hormone 17β-estradiol (E2) regulates many aspects of male and female physiology, it is described in the chemical indexes as a carcinogen. By the analysis of the literature, we unveil here a novel concept for which E2 possesses a dual nature for which it is both a toxic and a homeostatic regulator controlling DNA stability. Therefore, cancer could arise as a consequence of the deregulation of this delicate equilibrium between cellular pathways. 17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of "hormone" as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an "upgrade" to the vision of E2 as a "genotoxic hormone", which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects. [ABSTRACT FROM AUTHOR]

NIMA-related kinases, or NEKs, are a family of Ser/Thr protein kinases involved in cell cycle and mitosis, centrosome disjunction, primary cilia functions, and DNA damage responses among other biological functional contexts in vertebrate cells. In human cells, there are 11 members, termed NEK1 to 11, and the research has mainly focused on exploring the more predominant roles of NEKs in mitosis regulation and cell cycle. A possible important role of NEKs in DNA damage response (DDR) first emerged for NEK1, but recent studies for most NEKs showed participation in DDR. A detailed analysis of the protein interactions, phosphorylation events, and studies of functional aspects of NEKs from the literature led us to propose a more general role of NEKs in DDR. In this review, we express that NEK1 is an activator of ataxia telangiectasia and Rad3-related (ATR), and its activation results in cell cycle arrest, guaranteeing DNA repair while activating specific repair pathways such as homology repair (HR) and DNA double-strand break (DSB) repair. For NEK2, 6, 8, 9, and 11, we found a role downstream of ATR and ataxia telangiectasia mutated (ATM) that results in cell cycle arrest, but details of possible activated repair pathways are still being investigated. NEK4 shows a connection to the regulation of the nonhomologous end-joining (NHEJ) repair of DNA DSBs, through recruitment of DNA-PK to DNA damage foci. NEK5 interacts with topoisomerase IIβ, and its knockdown results in the accumulation of damaged DNA. NEK7 has a regulatory role in the detection of oxidative damage to telomeric DNA. Finally, NEK10 has recently been shown to phosphorylate p53 at Y327, promoting cell cycle arrest after exposure to DNA damaging agents. In summary, this review highlights important discoveries of the ever-growing involvement of NEK kinases in the DDR pathways. A better understanding of these roles may open new diagnostic possibilities or pharmaceutical interventions regarding the chemo-sensitizing inhibition of NEKs in various forms of cancer and other diseases. [ABSTRACT FROM AUTHOR]

The function of BRCA1/2 proteins is essential for maintaining genomic integrity in all cell types. However, why women who carry deleterious germline mutations in BRCA face an extremely high risk of developing breast and ovarian cancers specifically has remained an enigma. We propose that breast-specific epigenetic modifications, which regulate tissue differentiation, could team up with BRCA deficiency and affect tissue susceptibility to cancer. In earlier work, we compared genome-wide methylation profiles of various normal epithelial tissues and identified breast-specific methylated gene promoter regions. Here, we focused on deltaNp73, the truncated isoform of p73, which possesses antiapoptotic and pro-oncogenic functions. We showed that the promoter of deltaNp73 is unmethylated in normal human breast epithelium and methylated in various other normal epithelial tissues and cell types. Accordingly, deltaNp73 was markedly induced by DNA damage in human mammary epithelial cells (HMECs) but not in other epithelial cell types. Moreover, the induction of deltaNp73 protected HMECs from DNA damage-induced cell death, and this effect was more substantial in HMECs from BRCA1 mutation carriers. Notably, when BRCA1 was knocked down in MCF10A, a non-malignant breast epithelial cell line, both deltaNp73 induction and its protective effect from cell death were augmented upon DNA damage. Interestingly, deltaNp73 induction also resulted in inhibition of BRCA1 and BRCA2 expression following DNA damage. In conclusion, breast-specific induction of deltaNp73 promotes survival of BRCA1-deficient mammary epithelial cells upon DNA damage. This might result in the accumulation of genomic alterations and allow the outgrowth of breast cancers. These findings indicate deltaNp73 as a potential modifier of breast cancer susceptibility in BRCA1 mutation carriers and may stimulate novel strategies of prevention and treatment for these high-risk women. [ABSTRACT FROM AUTHOR]

Objective: Religious affiliation is inversely associated with alcohol dependence (AD). Our previous findings indicated that when a religious affiliation differentiated itself from cultural norms, then high-risk adolescents (those having parents with alcoholism history) raised with these affiliations exhibited fewer AD symptoms compared with adolescents of other religious affiliations and nonreligious adolescents. The first of two studies reported here provides a needed replication of our previous findings for childhood religious affiliation using a different sample, and the second study extends examination to current religious affiliation. Method: A national sample of male and female adolescents/young adults (N = 1,329; mean age = 19.6 years) was selected who were the offspring of members of the Vietnam Era Twin Registry. Parental alcoholism, religious affiliation types, and their interactions were examined as predictors of offspring AD symptoms. Results: (1) Offspring reared with a differentiating religious affiliation during child hood exhibited significantly fewer AD symptoms as young adults; (2) offspring with current differentiating religious affiliation also exhibited fewer AD symptoms; this main effect was not weakened by adding other measures of religiousness to the model; (3) differentiating religious affiliation was correlated with both family alcoholism risk and offspring outcome, and removed the association between family alcoholism risk and offspring outcome, thus indicating that differentiating religious affiliation was at least a partial mediator of the association between family AD history risk and offspring AD outcome. Conclusions: Current results indicate that religious differentiation is an inverse mediator of alcoholism risk for offspring with or without parental AD history and regardless of the influence of other religion variables. Results replicated our previous report on religious upbringing between ages 6 and 13 years and indicated an even stronger effect when current differentiating affiliation was examined., ALCOHOLISM RISK IS ASSOCIATED WITH specific family lineages (Cotton, 1979), and thus family studies have become an important component of alcoholism research (Hartman et al., 2006). These studies have shown [...]