Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic beta cells

Transgenic mice expressing simian virus 40 T antigen under control of the insulin gene regulatory region vary in their response to this protein. Each lineage is characteristically either tolerant to T antigen, or not, in which case autoantibodies arise with high frequency, and lymphocytes infiltrate and disrupt the pancreatic islets. Both non-tolerance and the autoimmune response appear to result from delayed onset of T antigen expression during beta cell development.     

Variant (6 ; 15) translocation in a murine plasmacytoma occurs near an immunoglobulin kappa gene but far from the myc oncogene

Chromosome translocations in B-lymphoid tumours are providing intriguing insights and puzzles regarding the role of immunoglobulin genes in the activation of the myc oncogene (reviewed in refs 1, 2). The 15 ; 12 translocations found in most murine plasmacytomas and the analogous 8 ; 14 translocation in human Burkitt's lymphomas involve scissions of murine chromosome 15 (human chromosome 8) near the 5' end of the c-myc gene and subsequent fusion near an immunoglobulin heavy-chain gene. The less well characterized 'variant' translocations found in about 15% of such tumours also involve the myc-bearing chromosome band, but exchange occurs with a chromosome bearing an immunoglobulin light-chain locus--in mice, the kappa-chain locus bearing chromosome 6 (refs 3-5) and, in man, chromosome 2 (or 22), at the same band at which the kappa (or lambda) locus lies (reviewed in ref. 1). The Burkitt variant translocations involve scissions 3' of c-myc; one 8 ; 22 translocation placed the C lambda locus just 3' of c-myc, but usually the chromosome 8 breakpoint is a greater, but unknown, distance away from c-myc, more than 20 kilobases (kb) in one 8 ; 2 translocation involving the C kappa gene. Little is known about the murine 6 ; 15 translocations, although a C kappa gene cloned from one plasmacytoma (PC7183) is linked, via chromosome 12 sequences, to an unidentified region of chromosome 15 (ref. 11). We describe here the chromosome fusion region from plasmacytoma ABPC4, which displays the typical reciprocal 6;15 translocations. We find that the chromosome 6 breakpoint is near C kappa but, unlike those in the heavy-chain locus, not at a position where immunoglobulin genes normally recombine. Moreover, the chromosome 15 sequences involved in the ABPC4 translocation are not derived from the vicinity of c-myc.     

A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse

The mouse mutation fragilitas ossium (fro) leads to a syndrome of severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Positional cloning of the locus identified a deletion in the gene encoding neutral sphingomyelin phosphodiesterase 3 (Smpd3) that led to complete loss of enzymatic activity. Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies.     

Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C

During spermatogenesis in the mammalian testis, stem cells (spermatogonia) differentiate into spermatocytes, which subsequently undergo two consecutive meiotic divisions to give rise to haploid spermatids. These cells are initially round but progressively elongate, condense their nuclei, acquire flagellar and acrosomal structures, and shed a significant amount of their cytoplasm to form spermatozoa (the sperm cells) in a developmental cascade termed spermiogenesis. Defects in these processes will lead to a lack of mature sperm cells (azoospermia), which is a major cause of male infertility in the human population. Here we report that a cell-surface protein of the immunoglobulin superfamily, junctional adhesion molecule-C (JAM-C), is critically required for the differentiation of round spermatids into spermatozoa in mice. We found that Jam-C is essential for the polarization of round spermatids, a function that we attribute to its role in the assembly of a cell polarity complex.     

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.     

科学新格局：英国科研及其国际合作

国际合作研究不仅可以利用其他国家的科研投资，而且能够产生具有轰动效应的创新型结果。由
于语言文化的相似性，英国与美国及欧洲国家有着较为广泛的联系，他们之间的合作是英国科学研究合作的
主体。随着科学研究及技术革新的发展更多地转向东方，以及中国和印度这两大科技力量的迅猛发展，英国
应该更加重视与这两个国家的合作。文章指出：应该就英国及其新伙伴之间的关系进行详细的研究，从而深
入理解中英两国间的合作并建立成功的合作模式。     

Hemodynamic patterns during fighting behaviour in the cat

Riassunto Durante il comportamento di lotta del gatto libero non anestetizzato si osserva tachicardia e aumento della gettata cardiaca; la pressione arteriosa e la conduttanza periferica totale variano relativamente poco. Si ha una marcata vasocostrizione mesenterica, mentre il letto iliaco subisce modificazioni di senso opposto a seconda dell'attività motoria dell'arto posteriore. In assenza di movimento si ha una vasocostrizione, che interessa non solo il letto cutaneo ma anche quello muscolare; questa vasocostrizione viene invece soffocata da una cospicua vasodilatazione, d'evidente origine metabolica, ogni qual volta vi sia attività muscolare locale.

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This research has been sponsored by the Air Force Office of Scientific Research, through the European Office of Aerospace Research (OAR), United States Air Force, under grant No. AF EOAR 67-41, and by Consiglio Nazionale delle Ricerche (Gruppo Nazionale di Medicina Sperimentale). Dr.Adams was a visiting investigator from Yale University, New Haven (Conn., USA), under a PHS post-graduate fellowship.