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Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3–H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegansortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3–H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.

AbstractThis paper summarises a ten-year conversation within London Journal of Primary Care about the nature of community-oriented integrated care (COIC) and how to develop and evaluate it. COIC means integration of efforts for combined disease-treatment and health-enhancement at local, community level. COIC is similar to the World Health Organisation concept of a Community-Based Coordinating Hub – both require a local geographic area where different organisations align their activities for whole system integration and develop local communities for health. COIC is a necessary part of an integrated system for health and care because it enables multiple insights into ‘wicked problems’, and multiple services to integrate their activities for people with complex conditions, at the same time helping everyone to collaborate for the health of the local population. The conversation concludes seven aspects of COIC that warrant further attention.

New genes contribute substantially to adaptive evolutionary innovation, but the functional evolution of new mammalian genes has been little explored at a broad scale. Previous work established mRNA-derived gene duplicates, known as retrocopies, as models for the study of new gene origination. Here we combine mammalian transcriptomic and epigenomic data to unveil the processes underlying the evolution of stripped-down retrocopies into complex new genes. We show that although some robustly expressed retrocopies are transcribed from preexisting promoters, most evolved new promoters from scratch or recruited proto-promoters in their genomic vicinity. In particular, many retrocopy promoters emerged from ancestral enhancers (or bivalent regulatory elements) or are located in CpG islands not associated with other genes. We detected 88–280 selectively preserved retrocopies per mammalian species, illustrating that these mechanisms facilitated the birth of many functional retrogenes during mammalian evolution. The regulatory evolution of originally monoexonic retrocopies was frequently accompanied by exon gain, which facilitated co-option of distant promoters and allowed expression of alternative isoforms. While young retrogenes are often initially expressed in the testis, increased regulatory and structural complexities allowed retrogenes to functionally diversify and evolve somatic organ functions, sometimes as complex as those of their parents. Thus, some retrogenes evolved the capacity to temporarily substitute for their parents during the process of male meiotic X inactivation, while others rendered parental functions superfluous, allowing for parental gene loss. Overall, our reconstruction of the “life history” of mammalian retrogenes highlights retroposition as a general model for understanding new gene birth and functional evolution.

The Clinical Pathway (in its complete definition Diagnostic, Clinical and Therapeutic Pathway - Percorso Diagnostico Terapeutico Assistenziale - PDTA), originally started to deal with the newly diagnosed hypertensive patient, developed also recommendations for the first-line drugs in case of specific indications/contraindications and organ damages. It has been developed by a working group of specialists in cardiology, nephrology, internal medicine (faculty included) designated by their hospitals (both public and private accredited), including all the main city hospitals, by general practitioners designated by the Medical Unions SNAMI, FIMMG, SMI and SiMI and by public health doctors belonging to the Local Health Unit of Milan, who have coordinated the proceedings and have guaranteed that possible conflicts of interest of single participants could not interfere with the PDTA, anyway approved by all in July 2009. The PDTA deals with the measuring and self- home-monitoring of blood pressure (BP) and the diagnosis of hypertension; it revises, sometimes “dries up” and rationalizes the recommendations for diagnostic tests and specialist evaluations; it develops prevention and non-pharmacological treatments, proposing also tools for patients and for prescribing correct nutrition and physical activity and a structured program for BP monitoring; but the main feature is the innovations brought in the proposed drug treatment in comparison with the current clinical practice.

The DREAM (dimerization partner [DP], retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell-cycle and other genes, but its mechanism of action is unclear. Here, we demonstrate that two C. elegansTHAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell-cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z, and we find that DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses germline-specific targets in the soma by facilitating H3K9me2 promoter marking. We further find that LIN-36 and LIN-15B differently regulate DREAM binding. In humans, THAP proteins have been implicated in cell-cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function.

On 9 September 2000, a meeting on General Practice/Family Medicine (GP/FM) in the Mediterranean was held at the 6th Mediterranean Congress in Malta. The creation of a Mediterranean GP/FM group was discussed among delegates from seven Mediterranean countries. Historical, cultural and epidemiological concepts supporting this initiative are presented. The main aims of this group and the key issues of the Malta consensus are clarified.

AbstractInteractive and multimedia methods are the future, already developing in teaching and learning modules in Medicine. It happens and has to happen because:1) It improves tools for the teacher in preparing and showing the bulk of materials on which students must study and learn; it enables interactivity with learners both in formative pathway and in final assessment.2) It improves attention, interest and involvement of students and learners, and acts as a guideline to progressive broadening in researches, studies, considerations, and information exchanges among different learners.3) The rapid progress in application of technology, WEB area and sources researches allows such a deepening and widening interactivity that before was never possible to imagine. It is the same thing also in CME, sometimes so dry, and dropped from above, while the new methodology may/must get rid of negative and boring features, often not useful in producing particular improvements in knowledge and quality.The Professional Doctor needs to feel a protagonist part in situation to be investigated, where interaction with all what media tools can offer may produce an “educative” improvement, much faster, effective and pleasant/rewarding.