Predictable acquisition of a new MHC recognition specificity following expression of a transfected T-cell receptor beta-chain gene

Activation of mature T lymphocytes requires specific corecognition of antigen together with membrane-associated glycoprotein products of the major histocompatibility complex (MHC). This dual specificity is determined by a single receptor structure consisting of a clone-specific alpha beta heterodimer. Because both the alpha and beta subunits possess unique combining-site-containing V regions, it remains an open issue as to what contribution each of the two chains of the receptor makes to the antigen versus MHC recognition specificities of the complete dimer present on any given T cell or in the T-cell pool as a whole. In the present work, we have used DNA-mediated gene transfer to express a new alpha or beta chain in a recipient murine T-cell hybridoma possessing a related antigen but distinct MHC specificity compared to the receptor-gene donor. Our results demonstrate that a beta-gene transfected hybridoma expresses new receptors with a predictable hybrid specificity, establishing that the beta chain has the predominant role in MHC molecule recognition in this model.     

A broad deglacial δ13C minimum event in planktonic foraminiferal records in the Okinawa Trough

The equatorial Pacific upwelling zone has been suspected of playing an important role in the global atmospheric CO2 changes associated with glacial-interglacial cycles.In order to assess the influencing scope of the surface water deglacial δ13C minimum in the tropical Iow-latitude Pacific,the core DGKS9603, collected from the middle Okinawa Trough, was examined for δ13C records of planktonic foraminifera N. dutertrei and G. ruber. The planktonic foraminiferal δ13C records show a clear decreasing event from 20 to 6 cal. kaBP., which is characterized by long duration of about 14 ka and amplitude shift of 0.4 × 10-3. Its minimum value occurred at 15.7 cai kaBP. The event shows fairly synchrony with the surface water deglacial δ13C minimum identiffed in the tropical Pacific and its marginal seas. Because there is no evidence in planktonic foraminiferal fauna and δ18O records for upwelling and river runoff enhancement,the broad deglacial δ13C minimum event in planktonic foraminiferal records revealed in core DGKS9603 might have been the direct influencing result of the deglacial surface water of the tropical Pacific. The identification for the event in the Okinawa Trough provides new evidence that the water evolution in the tropical low-latitude Pacific plays a key role in large regional, even global carbon cycle.     

Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.     

The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus.

T-associated maternal effect (Tme) is the only known maternal-effect mutation in the mouse. The defect is nuclear-encoded and embryos that inherit a deletion of the Tme locus from their mother die at day 15 of gestation. There are many genomically imprinted regions known in the mouse genome but so far no imprinted genes have been cloned. The Tme locus is absent in two chromosome-17 deletion mutants, Thp and the tLub2, and its position has been localized using these deletions to a 1-cM region. We report here that the genes for insulin-like growth factor type-2 receptor (Igf2r) and mitochondrial superoxide dismutase-2 (Sod-2) are absent from both deletions. Probes for these genes and for plasminogen (Plg) and T-complex peptide 1 (Tcp-1) were used in pulsed-field gel mapping to show that Tme must lie within a region of 800-1,100 kb. We also demonstrate that embryos express Igf2r only from the maternal chromosome, and that Tcp-1, Plg and Sod-2 are expressed from both chromosomes. Therefore Igf2r is imprinted and closely linked or identical to Tme.     

The genome of the social amoeba Dictyostelium discoideum

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.     

Specific reaction of aloe extract with serum proteins of various animals

Summary We found that aloe extract contains a lectin-like substance which reacts with serum proteins of various animals. Furthermore, in human serum 2 proteins,a ₂-macroglobulin anda ₁-antitrypsin, were shown to be reactive with aloe extract.     

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate.

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5 alpha-dihydrotestosterone (DHT).     

Evidences for the bipartite or diploid nuclei in conidia ofStreptomyces griseoflavus

Résumé 1^o L'étude cytologique a montré que les conidia deStreptomyces griseoflavus sont uninucléaires et que dans un conidium la substance chromatique a deux sphères durant la période qui précède sa maturation. 2^o L'inactivation par rayons-X des conidia donne des courbes du type «deux-coups (two-hit)». 3^o Dans le cas d'isolation des mutants biochimiques de conidia irradiés par rayons ultraviolets, on a trouvé une apparence de mutation retardée probablement à cause du délai de ségrégation. 4^o Le conidium de mutant venant d'auxotrophe par réversion comprend des unités génétiques hétérogènes.Ces quatre faits indiquent que les conidia de cette souche ont les nuclei bipartites ou diploides.     

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.