γ-Irradiation of malic acid in aqueous solutions

The -irradiation of malic acid in aqueous solutions was studied under initially oxygenated and oxygen-free conditions in an attempt to determine the possible interconversion of malic acid into other carboxylic acids, specifically those associated with Krebs cycle. The effect of dose on product formation of the system was investigated. Gas-liquid chromatography combined with mass spectrometry was used as the principal means of identification of the non-volatile products. Thin layer chromotography and direct probe mass spectroscopy were also employed.The findings show that a variety of carboxylic acids are formed, with malonic and succinic acids in greatest abundance. These products have all been identified as being formed in the -irradiation of acetic acid, suggesting a common intermediary. Since these molecules fit into a metabolic cycle, it is strongly suggestive that prebiotic pathways provided the basis for biological systems.     

The casein kinase I family: roles in morphogenesis.

Wnt signals play important roles in development and oncogenesis and are transduced through at least two pathways: a canonical beta-catenin-dependent and a beta-catenin-independent cascade. Casein kinase I (CKI) is required in both invertebrates and vertebrates to transduce canonical Wnt signals. However, its role in the beta-catenin-independent pathway was unknown. During vertebrate embryogenesis, the beta-catenin-independent cascade is thought to control cell movements and has been postulated to be analogous to the Drosophila planar cell polarity pathway, which signals through the JNK cascade. Here, we report that blocking CKI function inhibits embryonic morphogenesis and activates JNK in cell lines. These studies suggest that CKI might also act in the beta-catenin-independent pathway and indicate a role for CKI during convergence extension in early vertebrate development.     

Correcting for heterogeneity and non-comparability bias in multicenter clinical trials with a rescaled random-effect excess hazard model

In the presence of competing causes of event occurrence (e.g., death), the interest might not only be in the overall survival but also in the so-called net survival, that is, the hypothetical survival that would be observed if the disease under study were the only possible cause of death. Net survival estimation is commonly based on the excess hazard approach in which the hazard rate of individuals is assumed to be the sum of a disease-specific and expected hazard rate, supposed to be correctly approximated by the mortality rates obtained from general population life tables. However, this assumption might not be realistic if the study participants are not comparable with the general population. Also, the hierarchical structure of the data can induces a correlation between the outcomes of individuals coming from the same clusters (e.g., hospital, registry). We proposed an excess hazard model that corrects simultaneously for these two sources of bias, instead of dealing with them independently as before. We assessed the performance of this new model and compared it with three similar models, using extensive simulation study, as well as an application to breast cancer data from a multicenter clinical trial. The new model performed better than the others in terms of bias, root mean square error, and empirical coverage rate. The proposed approach might be useful to account simultaneously for the hierarchical structure of the data and the non-comparability bias in studies such as long-term multicenter clinical trials, when there is interest in the estimation of net survival.     

Preparation of Phgsphatioyll2-3Hjinositgl from Yeast Grown in Medium Containing N;Yol2-3Hjinositol

Phosphatidy[2-³]jinositol was prepared from Saccharoniycts cerevisiae (YSC-2), grown in synthetic meaiurn containing myo[2-³H]inositol. Over 44 μCi (or 81 %) of the racio-labeleo inositol was taken up by the organism, with 34 yCi incorporated into phospnatiaylinositol. Upon purification d) silicic acia-meaium pressure liquia chrcnatography (MPLC), a final yield of 24 to 2b μCi of phosphatiayl[2-³h]inositot with a specific radioactivity of 40 ± 10³ apm/nmoie wäs obtained. The purified phosphatiuyl[2-³H] inositol was founo to be a suitable substrate for phospholipase C from human platelets     

Trained Weakly-electric Fishes Pollimyrus isidori and Gnathonemus petersii (Mormyridae,Teleostei) Discriminate between Waveforms of Electric Pulse Discharges

Fish of the family Mormyridae emit weak, pulse-like electric organ discharges (EODs). The discharge rhythm is variable, but the waveform of the EOD is constant for each fish, with species- and individual characteristics. The ability of Pollimyrus isidori and Gnathonemus petersii (Mormyridae) to discriminate between different EOD waveforms was tested using a differential conditioning procedure. Fish were first trained to respond to a reference signal in swimming to a dish to receive a bloodworm (food reward). The reference signal consisted of a 10-Hz train of the digitally recorded EOD of a conspecific. Second, an alternative signal (10-Hz train of a different EOD, either from another species, or from a conspecific of the other sex) was associated with air bubbles as punishment. The two signals were played at successive trials in random order. On each trial the latency was measured between the onset of the signal and the response. 7 out of the 8 P. isidori tested and both of the two G. petersii tested associated the reference EOD with food. Among these, five P. isidori and two G. petersii responded differentially (p < 0.01) to EODs of different species. P. isidori similarly discriminated between conspecific EODs of different sexes. The quantity of different alternative EODs which could be tested was limited when fish eventually habituated to the punishment. Even when the amplitude of the EODs was randomly changed at each trial, two out of two G. petersii differentiated between EODs of the two species, and three out of three P. isidori tested differentiated between EODs within their own species. Response latencies to the rewarded signal during the basic training and during discrimination (when it had to be distinguished from the S-) were similar. G. petersii showed differential responses for S+ and S- also in the rhythm of discharge exhibited during playback, after five EOD pulses for one fish, and after a single pulse for the other. Mormyrids may therefore distinguish between conspecifics and members of other species, and even between individual conspecifics, by their EOD waveform.     

Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

ObjectivesTo assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development.DesignThis is a pre-specified secondary outcome from a randomised, clinical trial.SettingMaternity units and paediatric wards at three university hospitals in Denmark.ParticipantsChildren born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA < 37 weeks). There were 2129 children (71 premature) randomised to BCG and 2133 randomised (73 premature) to the control group.InterventionsBCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation.ResultsThe mean difference in ASQ score at 12 months adjusted for age and prematurity was -0.7 points (BCG vs. control, 95% confidence interval; -3.7 to 2.4), p = 0.67, corresponding to an effect size of Cohen’s d = -0.015 (-0.082 to 0.052). The mean difference in ASQ score for premature children at 22 months was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15).ConclusionsA negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01694108","term_id":"NCT01694108"}}NCT01694108     

Unlike effects of denervation on the rate of entry of inorganic phosphate into rat slow and fast muscles.

The increased inorganic phosphate flow, characteristic of denervated gastrocnemius muscle is shown to be present in additional denervated fast muscles, i.e. the plantaris, tibialis anterior and extensor digitorum longus muscles. The response of the soleus, a slow muscle, to denervation is biphasic. After an initial decrease of the phosphate flow at the end of the first postoperative day, there is a secondary rise which has the same general characteristics as the rise observed in fast muscles i.e. an exponential or hyperbolic increase to an asymptotic value reached after thirty days. The denervated fast and slow muscles are not converging to an intermediate metabolic pattern. The changes in phosphate flow induced by denervation are reversible in the soleus as well as in the gastrocnemius muscles.     

Continued mapping of chromosome 2 genes

This report describes our continued efforts to elucidate the genetic fine structure of the central portion of the mouse chromosome (Chr) 2. Mice from our panel of 28 Chr 2 congenic strains were tested: (1) for the presence of the antigens which stimulate Chr 2-reactive lymphocyte clones in mixed lymphocyte reactive lymphocyte clones in mixed lymphocyte reaction (MLR); (2) for the antigens of histocompatibility (H) genes H-42 ^a and H-45 ^a as determined by allograft rejection; and (3) for their ability to respond to the H-Y antigen in a cell-mediated lysis assay. The results obtained in this study have allowed additional mapping of immunoogically involved Chr 2 genes. The gene encoding the antigen which stimulates lymphocyte clone 1C11 can be considered wholly different from other Chr 2 H genes on the basis of chromosomal recombination. We have assigned the symbol H-48 to this gene. The following gene order has been established: [H-3, B2m, pa], we, [H-42, H-48], H-45, IR-H-Y, Hd-1, un, H-13, A ^w. The order of the bracketed genes is not known. H-44 maps centromeric to IR-H-Y. The genes encoding the antigens that stimulate lymphocyte clones 2G7, 2C10, 1F6, 1B10, and 1H10 map centromeric to H-45.