ß-Decay Half-Lives of 110 Neutron-Rich Nuclei across the N=82 Shell Gap: Implications for the Mechanism and Universality of the Astrophysical r Process.

The ß-decay half-lives of 110 neutron-rich isotopes of the elements from _{37}Rb to _{50}Sn were measured at the Radioactive Isotope Beam Factory. The 40 new half-lives follow robust systematics and highlight the persistence of shell effects. The new data have direct implications for r-process calculations and reinforce the notion that the second (A≈130) and the rare-earth-element (A≈160) abundance peaks may result from the freeze-out of an (n,γ)⇄(γ,n) equilibrium. In such an equilibrium, the new half-lives are important factors determining the abundance of rare-earth elements, and allow for a more reliable discussion of the r process universality. It is anticipated that universality may not extend to the elements Sn, Sb, I, and Cs, making the detection of these elements in metal-poor stars of the utmost importance to determine the exact conditions of individual r-process events.

Effect of age on bowel management in traumatic central cord syndrome.

STUDY DESIGN: A retrospective multicenter study. OBJECTIVES: To investigate the characteristics of bowel dysfunction in elderly people with traumatic central cord syndrome (TCCS). SETTING: A total of 28 Rosai hospitals in Japan. METHODS: The Rosai Hospital registry included 3006 persons with spinal cord injury during 1997-2007. The study subjects were 186 patients with TCCS (160 men, 26 women; mean age, 61.7±11.6 years, ±s.d.). Patients were divided according to age into the young group (<50 years, n=30), the middle-age group (50-69 years, n=112) and the elderly group (≥70 years, n=44). We assessed the differences in bowel management techniques (spontaneous, rectal medications and manual emptying) and activity of daily living (ADL) with respect to bowel care at discharge among the three groups. RESULTS: Continent spontaneous defecation was the most common bowel management method (50%, 93/186). The percentage of elderly subjects on continent spontaneous defecation (36.4%) was significantly less than that of the young group (66.7%; P<0.05). Furthermore, the percentage of elderly patients who required no bowel care (18.2%) was significantly less than those of the young (53.3%) and middle-age groups (41.1%; P<0.01). However, few differences in bowel care-related ADL were recognized among the three groups in patients who required manual emptying. CONCLUSION: The results identified significantly fewer patients aged ≥70 years with 'continent spontaneous defecation' or 'independent for bowel care' compared with younger patients. The results also highlighted the clinical importance of bowel dysfunction associated with TCCS especially in elderly people.

The spin temperature of NH3 in Comet C/1999S4 (LINEAR).

A high-dispersion spectrum of Comet C/1999S4 (LINEAR) was obtained in the optical region with the high-dispersion spectrograph on the Subaru telescope when the comet was 0.863 astronomical units from the Sun before its disintegration. We obtained high signal-to-noise ratio emission lines of the cometary NH2 bands from which an ortho-to-para ratio (OPR) of 3.33 +/- 0.07 was derived on the basis of a fluorescence excitation model. Assuming that cometary NH2 mainly originates from ammonia through photodissociation, the derived OPR of NH2 molecules should reflect that of ammonia, which provides information on the environment of molecular formation or condensation and of the thermal history of cometary ices. Assuming that the OPR of ammonia in comets was unchanged in the nucleus, the derived spin temperature of ammonia (28 +/- 2 kelvin) suggests that a formation region of the cometary ammonia ice was between the orbit of Saturn and that of Uranus in the solar nebula.

TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas.

TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene. Our results unexpectedly revealed a function independent of its transcriptional activity, as TTF-1 was found to interact with DDB1 and block its binding to CHK1, which in turn attenuated ubiquitylation and subsequent degradation of CHK1. Furthermore, TTF-1 overexpression conferred resistance to cellular conditions under DNA replication stress (RS) and prevented an increase in consequential DNA double-strand breaks, as reflected by attenuated induction of pCHK2 and γH2AX. Our findings suggest that the novel non-transcriptional function of TTF-1 identified in this study may contribute to lung adenocarcinoma development by conferring tolerance to DNA RS, which is known to be inherently elicited by activation of various oncogenes.

Antibodies to trophoblast in normal pregnant and secondary aborting women.

Enzyme-linked immunosorbent assays (ELISA) with the use of chorionic villous plasma membranes prepared from first trimester and term placentae were employed to detect antibodies to trophoblast in normal primigravid women. Normal pregnant women were found to produce IgG antibodies to trophoblast. These antibodies could be eluted from first trimester placentae. This antibody response was observed in the first trimester and gradually decreased as pregnancy progressed. IgM antibody responses were observed only in the third trimester. Antibodies in some primigravid women and secondary recurrent aborters showed allotypic reactivity with individual trophoblast membranes. This finding was confirmed by immunoblotting experiments in which antibodies from some normal pregnant women were shown to recognize the same trophoblast antigens as those recognized by antibodies from secondary recurrent spontaneous aborters.

Antigens of human trophoblast: trophoblast-lymphocyte cross-reactive antigens on platelets.

Human and rabbit antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens were employed in an enzyme-linked immunosorbent assay (ELISA) to identify and characterize the TLX alloantigen system on human platelets. Neither washing nor extraction in chaotrope or acid altered platelet TLX. The antigen was significantly changed by pronase and trypsin digestion, but Folch extraction yielded antigen in the hydrophilic interface, suggesting carbohydrate. Rabbit antibodies prepared to HLA-negative human syncytiotrophoblast TLX antigens were shown by platelet ELISA to have the same specificity and similar allotypy as anti-TLX antibodies from secondary (2 degrees) spontaneously aborting women. Patients with normal pregnancies before becoming 2 degrees aborters had both IgG and IgM antibodies to TLX. Anti-TLX in patients who never had a normal pregnancy were predominantly IgG. ELISA reactions performed with different concentrations of protein in the buffers detected anti-TLX activity in buffers containing high protein concentrations. This has been observed in studies of blocking antibodies in graft-versus-host disease and immune responses to tumor cells. Platelet TLX offers a new genetic and immunological approach to study similarities of the host-parasite relationships in pregnancy, transplantation, and cancer.

Trophoblast antigens in human seminal plasma.

Secondary recurrent spontaneous (2 degrees) aborters manifest persistent IgG, which show differential cytotoxicity patterns with lymphocytes from many donors. These are non-HLA-directed antibodies, which react allotypically with both trophoblast and lymphocytes. The antigens they recognize are designated trophoblast-lymphocyte crossreactive (TLX) antigens. Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma. The results showed 1) allotypic TLX antigens are present in seminal plasma; 2) seminal plasma TLX antigens may be membrane associated; 3) by immunoblotting, the molecular weights of antigens reactive with TLX antisera are 15, 22, 28, 33 kD and a smear between 180 and 340 kd; 4) by isoelectric focusing, TLX antigens show pI 4.0, 5.35, 5.9, 6.5, 6.8, and 7.2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity.

Isolation of a protease-deficient mutant of Bacillus brevis and efficient secretion of a fungal protein disulfide isomerase by the mutant.

The efficient production of a thermostable protein disulfide isomerase (PDI) was successfully achieved using the newly isolated protease-deficient mutant, Bacillus brevis 31-OK. Extracellular protease (exoprotease) activity was about a quarter of that in the parent, and the mutant was deficient in at least one of the major exoproteases. The cDNA encoding the fungal PDI was inserted downstream of the signal peptide-encoding region in an expression-secretion vector for B. brevis. Efficient production of PDI was feasible using B. brevis 31-OK as a host and modified signal sequences composed of three leucine residues inserted in the hydrophobic region of the MWP (middle wall protein) signal sequence. The maximal secretion of PDI into the culture medium was 1.1 g/l, which is about twice that by the parent strain and fifty times greater than the amount of rat and murine PDIs produced by Escherichia coli. The enzymatic properties such as the specific activity and thermal stability of the recombinant PDI are similar to those of natural PDI derived from Humicola insolens mycelia. B. brevis 31-OK was able to maintain its exoprotease activity at a low level throughout the cultivation and is considered to be useful host for production of a protease-sensitive protein and for increase of protein productivity due to stable accumulation.

[Combination therapy with irinotecan and CBDCA for patients in terminal stage of ovarian carcinoma].

Combination chemotherapy with irinotecan and CBDCA was performed for two patients in the terminal stage of ovarian carcinoma. Every week, 75 mg.m-2 of irinotecan and 75-100 mg.m-2 of CBD CA were intravenously administered. Both patients showed a partial response. Diarrhea was not a characteristic side effect of irinotecan in this case. Dose limiting factors were leucopenia and thrombocytopenia.

Supernovae and the chirality of the amino acids.

A mechanism for creating amino acid enantiomerism that always selects the same large-scale chirality is identified, and subsequent chemical replication and galactic mixing that would populate the Galaxy with the predominant species is described. This involves (1) the spin of the 14N in the amino acids, or in precursor molecules from which amino acids might be formed, that couples to the chirality of the molecules; (2) the neutrinos emitted from the supernova, together with the magnetic field from the nascent neutron star or black hole formed from the supernova, which selectively destroy one orientation of the 14N and thus select the chirality associated with the other 14N orientation; (3) chemical evolution, by which the molecules replicate and evolve to more complex forms of a single chirality on a relatively short timescale; and (4) galactic mixing on a longer timescale that mixes the selected molecules throughout the Galaxy.

TAK1 kinase determines TRAIL sensitivity by modulating reactive oxygen species and cIAP.

TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of cell death in several cancer cells, but many cells are resistant to TRAIL. The mechanism that determines sensitivity to TRAIL-killing is still elusive. Here we report that deletion of TAK1 kinase greatly increased activation of caspase-3 and cell death after TRAIL stimulation in keratinocytes, fibroblasts and cancer cells. Although TAK1 kinase is involved in NF-kappaB pathway, ablation of NF-kappaB did not alter sensitivity to TRAIL. We found that TRAIL could induce accumulation of reactive oxygen species (ROS) when TAK1 was deleted. Furthermore, we found that TAK1 deletion induced TRAIL-dependent downregulation of cIAP, which enhanced activation of caspase-3. These results show that TAK1 deletion facilitates TRAIL-induced cell death by activating caspase through ROS and downregulation of cIAP. Thus, inhibition of TAK1 can be an effective approach to increase TRAIL sensitivity.

Polyclonal activation of IgM antibodies to phospholipids in patients with idiopathic fetal growth retardation.

Phospholipid fractions and antibodies to phospholipids in the sera of normal pregnant women and patients with intra-uterine growth retardation (IUGR) were examined. Significant elevation of serum phospholipids were observed in the second and third trimesters of normal pregnancy. Serum concentration of phosphatidylserine and sphingomyelin was significantly lower in the third trimester in patients with IUGR than in normal pregnant women. Remarkable concentrations IgG and IgA antibodies to phospholipids were not observed in the patients or in normal pregnant women. Polyclonal activation of IgM antibodies was detected in normal pregnant women in the first and second trimesters but less so in the third. The activation of IgM antibodies was not observed in patients with IUGR induced by severe preeclampsia, but significant levels of IgM antibodies were detected in the third trimester in patients with idiopathic IUGR. It is suggested that antibody formation to phospholipids in normal pregnant women is induced by elevation of phospholipids and is down-regulated in the third trimester. Failure to down-regulate IgM antibodies may be related to the pathogenesis of idiopathic IUGR.

Studies on antilymphocyte antibodies in gestational choriocarcinoma.

The mixed lymphocyte reaction (MLR)-blocking activity of sera was examined in patients with gestational choriocarcinoma. The frequencies of human leukocyte antigens (HLAs) in seven choriocarcinoma patients and their husbands were not different from those in the normal Japanese population. In patients who were successfully treated, many mismatches were found between the woman's HLA-A, B, C antigens and those of her spouse. Sera from three patients showed cytotoxic activity against their husbands' T lymphocytes. Similar results were obtained with sera absorbed with platelets to test for cytotoxic activity against the husbands' B lymphocytes. Cytotoxic activity sometimes disappeared at the recovery stage of the disease. Significant MLR-blocking activity was found in sera of patients in a tumor-bearing stage, but was absent 3-4 months after serum human chorionic gonadotrophin levels dropped into the normal range. It reappeared when patients relapsed, showing that MLR-blocking activity reflected tumor burden. The MLR-blocking factors in patients' sera may not be identical to the so-called serum nonspecific immune inhibitor factors, but was specific to, or dependent on, the use of the husbands' lymphocytes as stimulator cells and was mediated by immunoglobulin (antibodies) reactive with antigens expressed on the husbands' B lymphocytes, e.g. the MHC class II antigens.

Blocking effects of maternal serum-IgG and placental eluate-IgG on materno-fetal mixed lymphocyte reaction and their individual specificity.

The purpose of this study is to clarify the problem regarding individual specificity of maternal serum immunoglobulin G (IgG) and placental eluate IgG that block the unidirectional mixed lymphocyte reaction (MLR) in which maternal and cord blood lymphocytes (lys) were used as responder and stimulator, respectively. Both maternal serum IgG and placental eluate IgG were found to include blocking antibodies (BA) which showed similar blocking effect on MLR. But, in the case of serum IgG, individual specificity of BA on MLR was observed to be less great in MLR done using whole lys or T-enriched lys of the cord blood as stimulator, whereas it became greatly significant when MLR was done using B-enriched lys of the cord blood as stimulator. This was the case even in MLR done by using unrelated maternal lys as responder. On the other hand, when in the case of placental eluate, it was found to be greater when compared to serum IgG even where MLR was done using not only B lys but also T lys as stimulator. It is thus strongly suggested that BA include individual specific antibodies against fetal B lys having HLA-D/DR locus determinants in addition to individually nonspecific antibodies common to pregnancy which may be produced to a "yet unknown fetal antigen."

Structure of a Ruminococcus albus endo-1,4-beta-glucanase gene.

A chromosomal DNA fragment encoding an endo-1,4-beta-glucanase I (Eg I) gene from Ruminococcus albus cloned and expressed in Escherichia coli with pUC18 was fully sequenced by the dideoxy-chain termination method. The sequence contained a consensus promoter sequence and a structural amino acid sequence. The initial 43 amino acids of the protein were deduced to be a signal sequence, since they are missing in the mature protein (Eg I). High homology was found when the amino acid sequence of the Eg I was compared with that of endoglucanase E from Clostridium thermocellum. Codon usage of the gene was not biased. These results suggested that the properties of the Eg I gene from R. albus was specified from the known beta-glucanase genes of the other organisms.

Efficient production of artificially designed gelatins with a Bacillus brevis system.

Artificially designed gelatins comprising tandemly repeated 30-amino-acid peptide units derived from human alphaI collagen were successfully produced with a Bacillus brevis system. The DNA encoding the peptide unit was synthesized by taking into consideration the codon usage of the host cells, but no clones having a tandemly repeated gene were obtained through the above-mentioned strategy. Minirepeat genes could be selected in vivo from a mixture of every possible sequence encoding an artificial gelatin by randomly ligating the mixed sequence unit and transforming it into Escherichia coli. Larger repeat genes constructed by connecting minirepeat genes obtained by in vivo selection were also stable in the expression host cells. Gelatins derived from the eight-unit and six-unit repeat genes were extracellularly produced at the level of 0.5 g/liter and easily purified by ammonium sulfate fractionation and anion-exchange chromatography. The purified artificial gelatins had the predicted N-terminal sequences and amino acid compositions and a solgel property similar to that of the native gelatin. These results suggest that the selection of a repeat unit sequence stable in an expression host is a shortcut for the efficient production of repetitive proteins and that it can conveniently be achieved by the in vivo selection method. This study revealed the possible industrial application of artificially designed repetitive proteins.

Meson Synchrotron Emission from Central Engines of Gamma-Ray Bursts with Strong Magnetic Fields.

Gamma-ray bursts (GRBs) are presumed to be powered by the still unknown central engines with timescales in the range from 1 ms to approximately a few seconds. We propose that the GRB central engines would be a viable site for strong meson synchrotron emission if they were compact astrophysical objects, such as neutron stars or rotating black holes with extremely strong magnetic fields (H approximately 1012-1017 G), and if protons or heavy nuclei were accelerated to ultrarelativistic energies on the order of approximately 1012-1022 eV. We show that the charged scalar mesons like pi+/- and heavy vector mesons like rho, which have several decay modes onto pi+/-, could be emitted, with a high intensity that is a thousand times larger than photons, through strong couplings to ultrarelativistic nucleons. These meson synchrotron emission processes eventually produce a burst of very high energy cosmic neutrinos with 1012 eV