Purine and pyrimidine metabolism: a firm basis for a transformed society

Purines and pyrimidines form the backbone of DNA and RNA. Hence, modification of purine and pyrimidine metabolism can have serious effects on normal functioning of a subject. These aspects formed the main topics for an International and a European Series of meetings, dedicated to the metabolism in man. In order to streamline the organization of these meetings the European Society was transformed to an International society: the Purine and Pyrimidine Society (www.ppsociety.org). This special issue of Nucleosides, Nucleotides, and, Nucleic, Acids highlights the last European meeting in Prague, focusing on inborn errors, cardiac diseases, inflammatory diseases, rheumatology, haematology, cancer, virology, genetic polymorphism, specific methodology, and, of course, metabolism. The meeting in Chicago in 2007 will be the first meeting of the Purine and Pyrimidine Society.     

Advances in purine and pyrimidine metabolism in health and diseases

ABSTRACT

In June, 2015, the Purine and Pyrimidine Society organized the 16th biennial symposium on Purine and Pyrimidine metabolism at the Faculty House of Columbia University, New York City. This exciting meeting focused on these important molecules, new developments in inborn errors of metabolism; therapeutic analogs. In addition, the biochemistry of mammalian and non-mammalian systems were discussed. Due to significant advances in molecular medicine, the boundaries between clinical and basic sciences have merged into exciting translational research, of which a small portion was highlighted in the presymposium.     

Novel Developments in Metabolic Disorders of Purine and Pyrimidine Metabolism and Therapeutic Applications of Their Analogs

The biennial 15^th symposium on Purine and Pyrimidine metabolism was held in Madrid, June 2013 (PP13). During the meeting, several novel developments on the diagnosis, pathophysiology, and treatment of several inborn errors of purine and pyrimidine metabolism were presented. These ranged from new drugs for gout to enzyme replacement therapies for mitochondrial diseases. A relatively novel aspect in this meeting was the interest in purine and pyrimidine metabolism in nonmammalian systems, such as parasites, mycoplasms, and bacteria. Development of novel analogs for parasite infections, cardiovascular diseases, inflammatory diseases, and cancer were also discussed.     

Advances in transgenic animal models and techniques

On May 11th and 12th 2017 was held in Nantes, France, the international meeting “Advances in transgenic animal models and techniques” (http://www.trm.univ-nantes.fr/). This biennial meeting is the fifth one of its kind to be organized by the Transgenic Rats ImmunoPhenomic (TRIP) Nantes facility (http://www.tgr.nantes.inserm.fr/). The meeting was supported by private companies (SONIDEL, Scionics computer innovation, New England Biolabs, MERCK, genOway, Journal Disease Models and Mechanisms) and by public institutions (International Society for Transgenic Technology, University of Nantes, INSERM UMR 1064, SFR François Bonamy, CNRS, Région Pays de la Loire, Biogenouest, TEFOR infrastructure, ITUN, IHU-CESTI and DHU-Oncogeffe and Labex IGO). Around 100 participants, from France but also from different European countries, Japan and USA, attended the meeting.     

A working hypothesis on the interdependent genesis of nucleotide bases,protein amino acids,and primitive genetic code

In the course of experimental approach to the chemical evolution in the primeval sea, we have found that the main products from formaldehyde and hydroxylamine are glycine, alanine, serine, aspartic acid etc., and the products from glycine and formaldehyde are serine and aspartic acid. Guanine is found in the two-letter genetic codons of all these amino acids.Based upon the finding and taking into consideration the probable synthetic pathways of nucleotide bases and protein amino acids in the course of chemical evolution and a correlation between the two-letter codons and the number of carbon atoms in the carbon skeleton of amino acids, 1 have been led to a working hypothesis on the interdependent genesis of nucleotide bases, protein amino acids, and primitive genetic code as shown in Table I.Protein amino acids can be classified into two groups: Purine Group amino acids and Pyrimidine Group amino acids. Purine bases and Pyrimidine bases are predominant in two-letter codons of amino acids belonging to the former and the latter group respectively.Guanine, adenine, and amino acids of the Purine Group may be regarded as synthesized from C₁ and C₂ compounds and N₁ compounds (including C₁N₁ compunds such as HCN), probably through glycine, in the early stage of chemical evolution.Uracil, cytosine, and amino acids of the Pyrimidine Group may be regarded as synthesized directly or indirectly from three-carbon chain compounds. This synthesis became possible after the accumulation of three-carbon chain compounds and their derivatives in the primeval sea.The Purine Group can be further classified into a Guanine or (Gly+nC₁) Subgroup and an Adenine or (Gly+nC₂) Subgroup or simply nC₂ Subgroup. The Pyrimidine Group can be further classified into a Uracil or C₃C₆C₉ Subgroup and a Cytosine or C₅-chain Subgroup (Table I).It is suggested that the primitive genetic code was established by a specific interaction between amino acids and their respective nucleotide bases. The interaction was dependent upon their concentration in the primeval environments and the binding constants between amino acids and their respective bases.Presented at the International Symposium (Lipmann Symposium) on The Concepts of Chemical Recognition in Biology held in Grignon near Versailles (France) on July 18–20, 1979.     

Novel targets for cancer and connective tissues diseases: A meeting sponsored by the International CCN Society

Abstracts

Novel targets for cancer and connective tissues diseases: A meeting sponsored by the International CCN Society Coast Coal Harbour Hotel, Vancouver, BC, Canada (September 24–27, 2011)     

The affinity of DNA sequences containing R5Y5 motif and TA repeats with 10.5-bp periodicity to histone octamer in vitro

Nucleosome positioning along the genome is partially determined by the intrinsic DNA sequence preferences on histone. RRRRRYYYYY (R5Y5, R?=?Purine and Y?=?Pyrimidine) motif in nucleosome DNA, which was presented based on several theoretical models by Trifonov et al., might be a facilitating sequence pattern for nucleosome assembly. However, there is not a high conformity experimental evidence to support the concept that R5Y5 motif is a key element for the determination of nucleosome positioning. In this work, the ability of the canonical, H2A.Z- and H3.3-containing octamers to assemble nucleosome on DNA templates containing R5Y5 motif and TA repeats within 10.5-bp periodicity was investigated by using salt-dialysis method in vitro. The results showed that the10.5-bp periodical distributions of both R5Y5 motif and TA repeats along DNA templates can significantly promote canonical nucleosome assembly and may be key sequence factors for canonical nucleosome assembly. Compared with TA repeats within 10.5-bp periodicity, R5Y5 motif in DNA templates did not elevate H2A.Z- and H3.3-containing nucleosome formation efficiency in vitro. This result indicates that R5Y5 motif probably isn’t a pivotal factor to regulate nucleosome assembly on histone variants. It is speculated that the regulatory mechanism of nucleosome assembly is different between canonical and variant histone. These conclusions can provide a deeper insight on the mechanism of nucleosome positioning.

Communicated by Ramaswamy H. Sarma     

Metaphycus parthenolecanii sp. n. (Hymenoptera: Encyrtidae), a parasitoid of Parthenolecanium corni (Hemiptera: Coccidae) in Iran

Metaphycus parthenolecanii Japoshvili sp. n. (Hymenoptera, Chalcidoidea, Encyrtidae), a parasitoid of the European fruit lecanium Parthenolecanium corni (Bouché, 1844) (Hemiptera, Coccoidea, Coccidae) in Iran, is described and illustrated.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:3B846DA1-7E97-442B-B4AF-B5C727A72521     

Heads in the clouds: On the carbon footprint of conference‐seeded publications in the advancement of knowledge

The carbon footprint of flying overseas to conferences, meetings, and workshops to share and build knowledge has been increasingly questioned over the last two decades, especially in environmental and climate sciences, due to the related colossal carbon emissions. Here, we infer the value of scientific meetings through the number of publications produced either directly or indirectly after attending a scientific conference, symposium, or workshop (i.e., the conference‐related production) and the number of publications produced per meeting (i.e., the conference‐related productivity) as proxies for the academic value of these meetings, and relate them to both the number of meetings attended and the related carbon emissions. We show that conference‐related production and productivity, respectively, increase and decay with the number of meetings attended, and noticeably that the less productive people exhibit the largest carbon footprint. Taken together, our results imply that a twofold decrease in the carbon footprint FCO2 of a given scientist would result in a twofold increase in productivity through a fivefold decrease in the number of meeting attended. In light of these figures, we call for both the implementation of objective and quantitative criteria related to the optimum number of conferences to attend in an effort to maximize scientific productivity while minimizing the related carbon footprint, and the development of a rationale to minimize the carbon emission related to scientific activities.     

2010 ASHG Awards and Addresses

Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the next pages, we have printed the Presidential Address and the addresses for the William Allan Award and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as webcasts of many other presentations, can be found at http://www.ashg.org.     

20th International Symposium on Shiftwork and Working Time: Biological Mechanisms,Recovery, and Risk Management in the 24-h Society

This dedicated issue of Chronobiology International is devoted to the selected proceedings of the 20th International Symposium on Shift Work and Working Time held in Stockholm, Sweden, 28 June to 1 July 2011. It constitutes the fifth such issue of the journal since 2004 dedicated to the selected proceedings to the meetings of the Working Time Society. The key theme of the 20th Symposium was “Biological Mechanisms, Recovery, and Risk Management in the 24-h Society.” The collection of papers of this dedicated issue represents the best of contemporary research on the effects of night and rotating shift schedules on worker health and safety. The contents cover such topics as sleep restriction, injuries, health, and performance of night work and rotating shiftwork, plus light treatment as a countermeasure against the circadian disruption of shiftwork. The majority of the papers are observational field studies, including some of large sample size, and three studies are well-designed laboratory experiments. (Author correspondence: goran.kecklund@stress.su.se)     

Women in cell biology: a seat at the table and a place at the podium

The Women in Cell Biology (WICB) committee of the American Society for Cell Biology (ASCB) was started in the 1970s in response to the documented underrepresentation of women in academia in general and cell biology in particular. By coincidence or causal relationship, I am happy to say that since WICB became a standing ASCB committee, women have been well represented in ASCB''s leadership and as symposium speakers at the annual meeting. However, the need to provide opportunities and information useful to women in developing their careers in cell biology is still vital, given the continuing bias women face in the larger scientific arena. With its emphasis on mentoring, many of WICB''s activities benefit the development of both men and women cell biologists. The WICB “Career Column” in the monthly ASCB Newsletter is a source of accessible wisdom. At the annual ASCB meeting, WICB organizes the career discussion and mentoring roundtables, childcare awards, Mentoring Theater, career-related panel and workshop, and career recognition awards. Finally, the WICB Speaker Referral Service provides a list of outstanding women whom organizers of scientific meetings, scientific review panels, and university symposia/lecture series can reach out to when facing the proverbial dilemma, “I just don''t know any women who are experts.”Although women are approaching parity in earning PhD and MD degrees, studies of their underrepresentation in academia, as principal investigators in funded science and in leadership positions, have led to the conclusion that gender schemas (Valian, 1999 ) work against women and diminish their success. This picture is supported by the National Academy of Sciences’ (NAS) report Beyond Bias and Barriers, which concludes that “Neither our academic institutions nor our nation can afford such underuse of precious human capital in science and engineering” (NAS, 2007 ) A New Yorker cartoon captures the scene at too many scientific gatherings (Figure 1).Open in a separate windowFIGURE 1:“The subject of tonight''s discussion is: Why are there no women on this panel?” Cartoon by David Sipress from The New Yorker Collection, www.cartoonbank.com. Used under Rights Managed License. Copyright holder Conde Nast.The Women in Cell Biology (WICB) committee was started in the early 1970s with notices of ad hoc meetings posted in women''s washrooms during the American Society for Cell Biology (ASCB) annual meeting and a mimeographed newsletter (Williams, 1996a , 1996b ). One goal for WICB''s “founding mothers” was to achieve more equitable representation as participants within ASCB, including more accurate representation of women within the ASCB leadership and as speakers. Consonant with this goal, WICB was delighted to become a standing committee of the ASCB in 1992. In the 30 years prior to this watershed date, only 13% of ASCB presidents were women. Since 1992, 50% of ASCB presidents have been women. I cannot determine whether this is causal, reflective of a third variable, or pure coincidence. But it is remarkable.The number of women leaders and speakers within ASCB suggests that WICB''s initial goal of more accurate representation of women has been largely achieved. However, the goals of helping women cell biologists successfully juggle career and family, find mentors, and achieve gender equity in job placement continue to be challenges. We have developed multiple WICB-sponsored activities throughout the year, and especially at the annual ASCB meeting, to give cell biologists tools with which to meet these challenges.     

2011 ASHG Awards and Addresses

Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of the Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the Presidential Address and the addresses for the William Allan and Curt Stern Awards. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.     

Floristic distinctiveness and endemic richness of woody plants highlight the biodiversity value of the herriza among all Mediterranean heathlands

Background: Heathlands are relatively abundant in the landscape of the western Mediterranean region, especially in the Strait of Gibraltar region, where it is locally known as herriza. They are associated with a mild Mediterranean climate regime and with acid, nutrient-poor soils. They harbour a high plant diversity, often viewed as a consequence of the transition between European Atlantic heathland and Mediterranean sclerophyllous shrubland floras.

Aims: To determine whether species-rich Mediterranean heathlands, including the herriza, constitute distinct heathland formations rather than transitional vegetation units between Atlantic heathlands and Mediterranean garrigue shrublands.

Methods: We quantified species richness, endemism and analysed the β-diversity of the woody component of Mediterranean heathland communities throughout its geographic range, with special emphasis on the Strait of Gibraltar region.

Results: Mediterranean heathlands, including the herriza, are not transitional communities between Atlantic heathlands and Mediterranean shrublands. Woody species richness and, particularly, endemic richness was the highest in the herriza.

Conclusions: The high biodiversity values of the herriza are a likely consequence of the ecological singularity of the Strait of Gibraltar region and its known role as a glacial refugium. Despite its treeless feature, the herriza deserves special recognition and protection from both in its European and North African extension.     

Taxonomic notes on Weissia subgenus Astomum,including Weissia wilsonii D.A.Callaghan,a new species from Europe

Introduction. The present study investigates the taxonomy of European members of Weissia Hedw. subgenus Astomum Hampe., a group considered taxonomically difficult and including species of high conservation concern.

Methods. A broad set of samples were subject to DNA sequencing and morphological analysis, plus a review of type material was undertaken.

Key Results and Conclusions. Three taxonomic additions and changes are supported. (1) Weissia longifolia var. angustifolia (Baumgartner) Crundw. & Nyholm is raised to species rank, W. angustifolia (Baumgartner) D.A.Callaghan, comb. et. stat. nov. (2) The type of W. multicapsularis (Sm.) Mitt. comprises an intermix of Phascum cuspidatum Hedw. and W. longifolia Mitt., and the protologue refers to unique features of P. cuspidatum but no such features of W. longifolia. Weissia multicapsularis is therefore described as a new synonym of P. cuspidatum. (3) Plants that have been named as W. multicapsularis by modern authors comprise an undescribed species, here named W. wilsonii D.A.Callaghan, sp. nov. An illustrated key to European species of Weissia subgenus Astomum is provided.     

Gout and Hyperuricemia in Japan: Perspectives for International Research on Purines and Pyrimidines in Man

One of the best-known disorders in purine metabolism is accumulation of uric acid leading to gout. Gout is a lifestyle disease, which was nicely illustrated in the joint symposium of the Japanese Society of Gout and Nucleic Acid Metabolism and of the Purine and Pyrimidine Society held in February 2011 in Tokyo, Japan. The westernization of the Japanese diet led to an increase in hyperuricemia in Japanese, which subsequently boosted research in this field, as illustrated in this symposium. As a consequence, Japanese nucleotide research also expanded, leading to the development of not only new drugs for treatment of gout, but also for other diseases such as cancer, viral infections, and cardiovascular diseases. The research on inborn errors led to the identification of various genetic polymorphisms affecting drug metabolism, revealing differences between Asians and non-Asians. Such genetic differences may also affect the enzymatic properties of an enzyme or a transporter, necessitating specific inhibitors. This knowledge will help to introduce personalization of treatment. In this symposium, the interaction between various specialties formed an excellent basis for translational research between these specialties but also from the bench to the clinic.     

Gout and hyperuricemia in Japan: perspectives for international research on purines and pyrimidines in man

One of the best-known disorders in purine metabolism is accumulation of uric acid leading to gout. Gout is a lifestyle disease, which was nicely illustrated in the joint symposium of the Japanese Society of Gout and Nucleic Acid Metabolism and of the Purine and Pyrimidine Society held in February 2011 in Tokyo, Japan. The westernization of the Japanese diet led to an increase in hyperuricemia in Japanese, which subsequently boosted research in this field, as illustrated in this symposium. As a consequence, Japanese nucleotide research also expanded, leading to the development of not only new drugs for treatment of gout, but also for other diseases such as cancer, viral infections, and cardiovascular diseases. The research on inborn errors led to the identification of various genetic polymorphisms affecting drug metabolism, revealing differences between Asians and non-Asians. Such genetic differences may also affect the enzymatic properties of an enzyme or a transporter, necessitating specific inhibitors. This knowledge will help to introduce personalization of treatment. In this symposium, the interaction between various specialties formed an excellent basis for translational research between these specialties but also from the bench to the clinic.     

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80?% of the mutant lines. In addition, 57?% of the lines were viable, 13?% subviable, 30?% embryonic lethal, and 7?% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model.