Spatiotemporal Organization of AT- and GC-rich DNA and Their Association With Transition Proteins TP1 and TP2 in Rat Condensing Spermatids

Transition protein 1 (TP1) and TP2 replace histones during midspermiogenesis (stages 12-15) and are finally replaced by protamines. TPs play a predominant role in DNA condensation and chromatin remodeling during mammalian spermiogenesis. TP2 is a zinc metalloprotein with two novel zinc finger modules that condenses DNA in vitro in a GC-preference manner. TP2 also localizes to the nucleolus in transfected HeLa and Cos-7 cells, suggesting a GC-rich preference, even in vivo. We have now studied the localization pattern of TP2 in the rat spermatid nucleus. Colocalization studies using GC-selective DNA-binding dyes chromomycin A3 and 7-amino actinomycin D and an AT-selective dye, 4',6-diamidino-2-phenylindole, indicate that TP2 is preferentially localized to GC-rich sequences. Interestingly, as spermatids mature, TP2 and GC-rich DNA moves toward the nuclear periphery, and in the late stages of spermatid maturation, TP2 is predominantly localized at the nuclear periphery. Another interesting observation is the mutually exclusive localization of GC- and AT-rich DNA in the elongating and elongated spermatids. A combined immunofluorescence experiment with anti-TP2 and anti-TP1 antibodies revealed several foci of overlapping localization, indicating that TP1 and TP2 may have concerted functional roles during chromatin remodeling in mammalian spermiogenesis.

Juutalaisvastaisuus suomalaisissa aikakauslehdissä ja kirjallisuudessa 1918-1944

Anti-Semitism existed in Finland during the whole period covered by this study. The immoral acts associated with Jews in the articles were mostly regarded as universal habits, qualities and/or modes of action, that is, unconnected with any particular Finnish Jew. Researchers have tried to explain anti-Semitism in several ways. The theory of Jews as outsiders has been a popular explanation as well as xenophobia, chimerical anti-Semitism and the socio-economic models. The main sources of this study have been over 400 Finnish periodicals and magazines, literature and text books published between 1918 and 1944. This vast number of magazines includes those of the army and the civil guard, religion, humour and the papers of the Finnish extreme right. One can see a distinct foreign and especially German influence in the subjects and phraseology of Finnish anti-Semitic writings between 1918 and 1944. Several known Finnish anti-Semitic writers had some kind of link with Germany. Some Finnish organisations and societies were openly anti-Semitic during this period. There had been cycles in the activity of anti-Semitic writing in Finland, obvious peaks appearing in 1918 1919, 1929 1931, 1933 1938 and 1942 1944. The reason for the 1918 1919 activity was the civil rights which were granted to the Jews in Finland, and the Russian Bolshevik revolution. The worldwide depression from 1929 to 1932 seem to be the reason for new anti-Semitic writing activity. The rise of National Socialism in Germany and the influence this phenomenon had in Finland was the reason for the peak during 1933 1938. During the continuation war 1942 1944 National Socialist Germany was fighting side-by-side with Finland and their anti-Semitic propaganda found easier access to Finland. Of the 433 magazines, journals and newspapers which were used in this study, 71 or 16.4 per cent had at least one article that can be identified as anti-Semitic; especially the magazines of national socialists and other extreme right parties were making anti-Semitic annotations. There were about 50 people known to have written anti-Semitic articles. At least half of these known writers had studied at the university, including as many as 10 priests. Over and above these, there was an even larger number of people who wrote under a pseudonym. The material used suggested that anti-Semitism was not very popular in Finland between 1918 and 1944. Anti-Semitic articles appeared mostly in the magazines of the extreme right, but their circulation was not very large. A proof of the slight influence of these extreme right anti-Semitic ideas is that, beside the tightening of policy towards Jewish immigrants in 1938 and the handing over of eight of these refugees to Germany in 1942, the official policy of Finland never became anti-Semitic. As was stated before, despite the cycles in the number of writings, there does not appear to have been any noticeable change in public opinion. One must also remember that most Finns had not at that period actually met a Jew. The material used suggests that between 1918 and 1944 the so-called Jewish question was seemingly unimportant for most Finns and their attitude to Jews and Jewishness can be described as neutral.

The Vexing Case of Igor Shafarevich, a Russian Political Thinker

The Russian mathematician, academician and former dissident Igor Shafarevich (b. 1923) is commonly mentioned in Western scholarly studies on perestroika and post-perestroika-era Russian politics as one of the most notable anti-Semites and extreme nationalists of the country. This notoriety owes to Shafarevich’s old samizdat article Russophobia, which was published in 1988. The scandal surrounding Russophobia came to a head when the president of The National Academy of Sciences in the United States asked Shafarevich, its honorary member, to resign. Nothing like this had ever happened in the academy’s history. The present dissertation discusses Shafarevich’s political activities, his texts and ideas as well as their reception. Particular attention is given to Russophobia, whose detailed examination proves very clearly that its reputation as an anti-Semitic text is groundless. The reasons for Russophobia’s hasty but fierce condemnation were many, but only one was that when the Soviet system began to tumble, it was commonly assumed that a vigorous rise in anti-Semitism and extreme nationalism in the Soviet Union/Russia would be just a matter of time. Many observers were highly sensitised to detecting its signs and symptoms. The dissertation also shows that most of those to write the first criticisms of Russophobia and to liken Shafarevich to the ideologues of Nazi Germany were the same people he had criticised in Russophobia for their deterministic view of history and irrational manner of connecting things for the purpose of fanning the flames of distrust between Russia’s Jews and Russians. In retrospect, it is fairly evident that Shafarevich actually managed to effectively “neutralise” the message of many of those obsessed with the Jews among his Russian contemporaries and contributed to the fact that anti-Jewish sentiments have been a great deal less popular in post-communist Russia than so many had feared and expected. The thesis also thoroughly discusses Shafarevich’s other texts and activities before Russophobia’s appearance and after it. In the 1970s, Shafarevich was one of the best-known dissidents in the Soviet Union. He worked together with academician Andrei Sakharov in a dissidents’ unofficial human rights committee and co-operated closely with Aleksandr Solzhenitsyn before Solzhenitsyn’s exile. Then, during the chaotic years of perestroika, Shafarevich defended the basic rights of ordinary citizens and warned that the hype concerning democracy could become counterproductive if the most palpable result of the reforms was the disappearance of citizens’ basic security and elementary social justice. One of the conclusions of the thesis is that even if the world around Shafarevich has changed considerably, his views have remained essentially the same since the late 1960s and early 1970s.

Reconstituting identity and history in post-war Mostar, Bosnia-Herzegovina

This paper by Carl Grodach demonstrates the careful unravelling of complexity, diversity, contestation and contradictions involved in the reconstruction of symbolic urban spaces after violent conflict, and the allied processes of cultural reinterpretation, political reconfiguration and material revaluation which accompany it. The paper analyses the reconstruction and redevelopment of the 16th-century historic centre of Mostar, Bosnia-Herzegovina, following the Bosnian Wars of 1992–1995. Reconstruction efforts centre around Stari Most, the 16th-century Ottoman bridge destroyed by Bosnian Croat military in 1993. In Mostar, both international and local organizations are in the process of reinterpreting Bosnia’s legacy of Ottoman city spaces. This research and analysis illuminates how such spaces can be central to contemporary projects to redefine group identities and conceptions of place. It provides insight into the ways various groups are attempting to reshape outside perceptions of the city—and Bosnia’s ethnic conflict—to articulate a new definition of local identity and ethnic relations and to remake a stable tourist economy through Mostar’s urban spaces.

Immunological studies on nucleic-acids and their components .6. Antibodies specific to two deoxyribotrinucleotide sequences

Antibodies to the deoxyribotrinucleotides dpApTpA and dpApApT were prepared by injecting the bovine serum albumin conjugates of the respective haptens in rabbits. The specificities of the antibodies were determined by estimating the inhibition of the binding of the tritiated haptens to the immunoglobulins by various nonradioactive mono- and oligonucleotides, using nitrocellulose membrane binding assay. Anti-dpApTpA and anti-dpApApT antisera were found to contain antibodies which were highly specific to the respective hapten sequence.

Diversity in the Early Years: Intercultural Learning and Teaching

"New global contexts are presenting new challenges and new possibilities for young children and those around them. Climate change, armed conflict and poverty combine with new frontiers of discovery in science and technology to create a paradoxical picture of both threat and opportunity for our world and our children. On the one hand, children are experiencing unprecedented patterns of disparity and inequity; yet, on the other hand, they have seemingly limitless possibilities to engage with new technologies and social processes. Seismic shifts such as these are inviting new questions about the conditions that young children need to learn and thrive. Diversity in the Early Years: Intercultural Learning and Teaching explores significant aspects of working with children and adults from diverse backgrounds. It is a valuable resource for teaching early childhood pre-service teachers to raise awareness about issues of diversity - whether diversity of culture, language, education and/or gender - and for helping them to develop their own pedagogical approaches to working with diverse populations."--Publisher website

Mutational analysis of active-site residues in the Mycobacterium leprae RecA intein, a LAGLIDADG homing endonuclease: Asp(122) and Asp(193) are crucial to the double-stranded DNA cleavage activity whereas Asp(218) is not

Mycobacterium leprae recA harbors an in-frame insertion sequence that encodes an intein homing endonuclease (PI-MleI). Most inteins (intein endonucleases) possess two conserved LAGLIDADG (DOD) motifs at their ctive center. A common feature of LAGLIDADG-type homing endonucleases is that they recognize and cleave the same or very similar DNA sequences. However, PI-MleI is distinctive from other members of the family of LAGLIDADG-type HEases for its modular structure with functionally separable domains for DNA-binding and cleavage, each with distinct sequence preferences. Sequence alignment analyses of PI-MleI revealed three putative LAGLIDADG motifs; however, there is conflicting bioinformatics data in regard to their identity and specific location within the intein polypeptide. To resolve this conflict and to determine the active-site residues essential for DNA target site recognition and double-stranded DNA cleavage, we performed site-directed mutagenesis of presumptive catalytic residues in the LAGLIDADG motifs. Analysis of target DNA recognition and kinetic parameters of the wild-type PI-MleI and its variants disclosed that the two amino acid residues, Asp(122) (in Block C) and Asp(193) (in functional Block E), are crucial to the double-stranded DNA endonuclease activity, whereas Asp(218) (in pseudo-Block E) is not. However, despite the reduced catalytic activity, the PI-MleI variants, like the wild-type PI-MleI, generated a footprint of the same length around the insertion site. The D122T variant showed significantly reduced catalytic activity, and D122A and D193A mutations although failed to affect their DNA-binding affinities, but abolished the double-stranded DNA cleavage activity. On the other hand, D122C variant showed approximately twofold higher double-stranded DNA cleavage activity, compared with the wild-type PI-MleI. These results provide compelling evidence that Asp(122) and Asp(193) in DOD motif I and II, respectively, are bona fide active-site residues essential for DNA cleavage activity. The implications of these results are discussed in this report.

Prognostic molecular factors and algorithms in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin lymphomas. As DLBCL is characterized by heterogeneous clinical and biological features, its prognosis varies. To date, the International Prognostic Index has been the strongest predictor of outcome for DLBCL patients. However, no biological characters of the disease are taken into account. Gene expression profiling studies have identified two major cell-of-origin phenotypes in DLBCL with different prognoses, the favourable germinal centre B-cell-like (GCB) and the unfavourable activated B-cell-like (ABC) phenotypes. However, results of the prognostic impact of the immunohistochemically defined GCB and non-GCB distinction are controversial. Furthermore, since the addition of the CD20 antibody rituximab to chemotherapy has been established as the standard treatment of DLBCL, all molecular markers need to be evaluated in the post-rituximab era. In this study, we aimed to evaluate the predictive value of immunohistochemically defined cell-of-origin classification in DLBCL patients. The GCB and non-GCB phenotypes were defined according to the Hans algorithm (CD10, BCL6 and MUM1/IRF4) among 90 immunochemotherapy- and 104 chemotherapy-treated DLBCL patients. In the chemotherapy group, we observed a significant difference in survival between GCB and non-GCB patients, with a good and a poor prognosis, respectively. However, in the rituximab group, no prognostic value of the GCB phenotype was observed. Likewise, among 29 high-risk de novo DLBCL patients receiving high-dose chemotherapy and autologous stem cell transplantation, the survival of non-GCB patients was improved, but no difference in outcome was seen between GCB and non-GCB subgroups. Since the results suggested that the Hans algorithm was not applicable in immunochemotherapy-treated DLBCL patients, we aimed to further focus on algorithms based on ABC markers. We examined the modified activated B-cell-like algorithm based (MUM1/IRF4 and FOXP1), as well as a previously reported Muris algorithm (BCL2, CD10 and MUM1/IRF4) among 88 DLBCL patients uniformly treated with immunochemotherapy. Both algorithms distinguished the unfavourable ABC-like subgroup with a significantly inferior failure-free survival relative to the GCB-like DLBCL patients. Similarly, the results of the individual predictive molecular markers transcription factor FOXP1 and anti-apoptotic protein BCL2 have been inconsistent and should be assessed in immunochemotherapy-treated DLBCL patients. The markers were evaluated in a cohort of 117 patients treated with rituximab and chemotherapy. FOXP1 expression could not distinguish between patients, with favourable and those with poor outcomes. In contrast, BCL2-negative DLBCL patients had significantly superior survival relative to BCL2-positive patients. Our results indicate that the immunohistochemically defined cell-of-origin classification in DLBCL has a prognostic impact in the immunochemotherapy era, when the identifying algorithms are based on ABC-associated markers. We also propose that BCL2 negativity is predictive of a favourable outcome. Further investigational efforts are, however, warranted to identify the molecular features of DLBCL that could enable individualized cancer therapy in routine patient care.

A CD8(+) T cell clone specific for antigen also recognizes peptidomimics present in anti-idiotypic antibody: Implications for T cell memory

The relay hypothesis [R. Nayak, S. Mitra-Kaushik, M.S. Shaila, Perpetuation of immunological memory: a relay hypothesis, Immunology 102 (2001) 387-395] was earlier proposed to explain perpetuation of immunological memory without requiring long lived memory cells or persisting antigen. This hypothesis envisaged cycles of interaction and proliferation of complementary idiotypic B cells (Burnet cells) and anti-idiotypic B cells (Jerne cells) as the primary reason for perpetuation of immunological memory. The presence of pepti-domimics of antigen in anti-idiotypic antibody and their presentation to antigen specific T cells was postulated to be primary reason for perpetuation of T cell memory. Using a viral hemagglutinin as a model, in this work, we demonstrate the presence of peptidomimics in the variable region of ail anti-idiotypic antibody capable of functionally mimicking the antigen derived peptides. A CD8(+) CTL clone was generated against the hemagglutinin protein which specifically responds to either peptidomimic synthesizing cells or peptidomimic pulsed antigen presenting cells. Thus, it appears reasonable that a population of activated antigen specific T cells is maintained in the body by presentation of peptidomimic through Jerne cells and other antigen presenting cells long after immunization. (C) 2007 Elsevier Inc. All rights reserved.

Impact of chemotherapy on cancer-related fatigue and cytokines in 1312 patients: A systematic review of quantitative studies

Purpose of review: Cancer-related fatigue (CRF) is the most common psychosomatic distress experienced by cancer patients before, during and after chemotherapy. Its impact on functional status and Health Related Quality of Life is a great concern among patients, healthcare professionals and researchers. The primary objective of this systematic review is to determine whether the different chemotherapies affect the association of CRF with individual pro- and anti-inflammatory cytokines. The PRISMA statement guideline has been followed to systematically search and screen article from PubMed and Embase. Recent findings: This review has examined 14 studies which included a total of 1312 patients. These studies assayed 20 different kinds of cytokines. The cytokines interleukin-6, interleukin-1RA, TGF-[beta] and sTNF-R2 were associated with CRF in patients receiving anthracycline-based chemotherapy. However, only interleukin-13 was identified in the taxane-based chemotherapy. Similarly, different sets of cytokines were linked with CRF in patients with chemotherapy regimens containing platinum, cyclophosphamides, topotecan or bleomycin. Summary: This review has identified that cytokines are differentially linked with CRF according to the various types of chemotherapy regimens.

Perpetuation of immunological memory through common MHC-I binding modes of peptidomimic and antigenic peptides

Understanding the molecular mechanisms of immunological memory assumes importance in vaccine design. We had earlier hypothesized a mechanism for the maintenance of immunological memory through the operation of a network of idiotypic and anti-idiotypic antibodies (Ab2). Peptides derived from an internal image carrying anti-idiotypic antibody are hypothesized to facilitate the perpetuation of antigen specific T cell memory through similarity in peptide-MHC binding as that of the antigenic peptide. In the present work, the existence of such peptidomimics of the antigen in the Ab2 variable region and their similarity of MHC-I binding was examined by bioinformatics approaches. The analysis employing three known viral antigens and one tumor-associated antigen shows that peptidomimics from Ab2 variable regions have structurally similar MHC-I binding patterns as compared to antigenic peptides, indicating a structural basis for memory perpetuation. (C)) 2007 Elsevier Inc. All rights reserved.

Stimulating immune responses to fight cancer: Basic biology and mechanisms

Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro-inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen-specific T-cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 (PD-1) receptor and its ligands (PD-L1, PD-L2) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Researchers have developed anti-PD-1 and anti-PDL-1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor-infiltrating T-cells. These are currently being studied in lung cancer. Likewise, CTLA-4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.

Trade wars in the TRIPS Council: Intellectual property, technology transfer, and climate change

This Chapter considers the geopolitical conflicts in respect of intellectual property, trade, and climate change in the TRIPS Agreement 1994 under the World Trade Organization (WTO). In particular, it focuses upon debates in the TRIPS Council on the topic of patent law and clean energy in 2013 and 2014. The chapter highlights the development agenda of a number of developing countries who are keen for access to clean energy to combat climate change and global warming. It also considers the mixed contributions of members of the BRICS/ BASIC group – including Brazil, India, China, and South Africa. This chapter highlights the intellectual property maximalist position of a number of developed countries on intellectual property, climate change, and trade. Seeking to overcome this conflict and stalemate, this Chapter puts forward both procedural and substantial reform options in respect of intellectual property, trade, and climate change in the TRIPS Council and the WTO. It also flags that the TRIPS Agreement 1994 could well be displaced by the rise of mega-regional trade agreements – such as the Trans-Pacific Partnership (TPP), and the Trans-Atlantic Trade and Investment Partnership (TTIP).

Efficacy of family mediation and the role of family violence: Study protocol

Background Family law reforms in Australia require separated parents in dispute to attempt mandatory family dispute resolution (FDR) in community-based family services before court attendance. However, there are concerns about such services when clients present with a history of high conflict and family violence. This study protocol describes a longitudinal study of couples presenting for family mediation services. The study aims to describe the profile of family mediation clients, including type of family violence, and determine the impact of violence profiles on FDR processes and outcomes, such as the type and durability of shared parenting arrangements and clients’ satisfaction with mediated agreements. Methods A mixed method, naturalistic longitudinal design is used. The sampling frame is clients presenting at nine family mediation centres across metropolitan, outer suburban, and regional/rural sites in Victoria, Australia. Data are collected at pre-test, completion of mediation, and six months later. Self-administered surveys are administered at the three time points, and a telephone interview at the final post-test. The key study variable is family violence. Key outcome measures are changes in the type and level of acrimony and violent behaviours, the relationship between violence and mediated agreements, the durability of agreements over six months, and client satisfaction with mediation. Discussion Family violence is a major risk to the physical and mental health of women and children. This study will inform debates about the role of family violence and how to manage it in the family mediation context. It will also inform decision-making about mediation practices by better understanding how mediation impacts on parenting agreements, and the implications for children, especially in the context of family violence.

Disarming identities : Ethnic identities in conflict resolution: Hindrance or helpful resource?

This thesis proposes that national or ethnic identity is an important and overlooked resource in conflict resolution. Usually ethnic identity is seen both in international relations and in social psychology as something that fuels the conflict. Using grounded theory to analyze data from interactive problem-solving workshops between Palestinians and Israelis a theory about the role of national identity in turning conflict into protracted conflict is developed. Drawing upon research from, among others, social identity theory, just world theory and prejudice it is argued that national identity is a prime candidate to provide the justification of a conflict party’s goals and the dehumanization of the other necessary to make a conflict protracted. It is not the nature of national identity itself that lets it perform this role but rather the ability to mobilize a constituency for social action (see Stürmer, Simon, Loewy, & Jörger, 2003). Reicher & Hopkins (1996) have demonstrated that national identity is constructed by political entrepreneurs to further their cause, even if this construction is not a conscious one. Data from interactive problem-solving workshops suggest that the possibility of conflict resolution is actually seen by participants as a direct threat of annihilation. Understanding the investment necessary to make conflict protracted this reaction seems plausible. The justification for ones actions provided by national identity makes the conflict an integral part of a conflict party’s identity. Conflict resolution, it is argued, is therefore a threat to the very core of the current national identity. This may explain why so many peace agreements have failed to provide the hoped for resolution of conflict. But if national identity is being used in a constructionist way to attain political goals, a political project of conflict resolution, if it is conscious of the constructionist process, needs to develop a national identity that is independent of conflict and therefore able to accommodate conflict resolution. From this understanding it becomes clear why national identity needs to change, i.e. be disarmed, if conflict resolution is to be successful. This process of disarmament is theorized to be similar to the process of creating and sustaining protracted conflict. What shape and function this change should have is explored from the understanding of the role of national identity in supporting conflict. Ideas how track-two diplomacy efforts, such as the interactive problem-solving workshop, could integrate a process by both conflict parties to disarm their respective identities are developed.