Interactions of glucose, acetoacetate and insulin in mammary-gland slices of lactating rats.

1. Utilization of 5mM-glucose by slices of lactating mammary gland was decreased 33% on addition of acetoacetate (2mM) to the incubation medium. This inhibition was accompanied by increases in the intracellular concentrations of citrate and glucose 6-phosphate. 2. In the presence of acetoacetates the accumulation of pyruvate in the medium approximately doubled. 3. Insulin completely reversed the inhibitory effect of acetoacetates on glucose utilization, without altering the amount of acetoacetate removed or pyruvate formed. 4. Similar results were obtained with mammary-gland slices from diabetic rats, except that insulin did not completely reverse the effects of acetoacetates. 5. Acetoacetate inhibited the formation of 14CO2 from [1-14C]pyruvate; this effect was not overcome by insulin. 6. Insulin increased the proportion of [3-14C]acetoacetate that was converted into lipid and decreased that oxidized to CO2.7. The physiological significance of these findings is discussed.     

Thymidine uptake and utilization in Escherichia coli: a new gene controlling nucleoside transport.

A commonly used strain of Escherichia coli K-12 was shown to be deficient in the transport of a number of nucleosides, including thymidine. Thymidine incorporation was unaffected. Strain AB2497 exhibited a strikingly lower thymidine pulse-label incorporation at low (less than 1 mug/ml) thymidine concentrations than do many other strains. The deficiency appeared to be due to mutation in a single gene. This gene, which we designated nup (for nucleoside uptake), is located at 10 to 13 min on the E. coli linkage map. In nup+ strains, the transport of a given nucleoside was relatively insensitive to large excesses of other nucleosides but was competitively inhibited by the same nucleoside. Mutants deficient inthymidine kinase are deficient in thymidine uptake but normal in deoxyadenosine uptake. A two-step model for nucleoside transport is presented in which the first step, utilizing the nup gene product, is a nonspecific translocation of nucleoside to the interior of the cell. In the second step, the individual nucleosides are modified by cellular enzymes (e.g., nucleosides kinases) facilitate accumulation.     

Climate variability and campylobacter infection: an international study

Campylobacter is among the most important agents of enteritis in developed countries. We have described the potential environmental determinants of the seasonal pattern of infection with campylobacter in Europe, Canada, Australia and New Zealand. Specifically, we investigated the role of climate variability on laboratory-confirmed cases of campylobacter infection from 15 populations. Regression analysis was used to quantify the associations between timing of seasonal peaks in infection in space and time. The short-term association between weekly weather and cases was also investigated using Poisson regression adapted for time series data. All countries in our study showed a distinct seasonality in campylobacter transmission, with many, but not all, populations showing a peak in spring. Countries with milder winters have peaks of infection earlier in the year. The timing of the peak of infection is weakly associated with high temperatures 3 months previously. Weekly variation in campylobacter infection in one region of the UK appeared to be little affected by short-term changes in weather patterns. The geographical variation in the timing of the seasonal peak suggests that climate may be a contributing factor to campylobacter transmission. The main driver of seasonality of campylobacter remains elusive and underscores the need to identify the major serotypes and routes of transmission for this disease.     

Incorporating patterns of disperser behaviour into models of seed dispersal and its effects on estimated dispersal curves

The processes determining where seeds fall relative to their parent plant influence the spatial structure and dynamics of plant populations and communities. For animal dispersed species the factors influencing seed shadows are poorly understood. In this paper we test the hypothesis that the daily temporal distribution of disperser behaviours, for example, foraging and movement, influences dispersal outcomes, in particular the shape and scale of dispersal curves. To do this, we describe frugivory and the dispersal curves produced by the southern cassowary, Casuarius casuarius, the only large-bodied disperser in Australia’s rainforests. We found C. casuarius consumed fruits of 238 species and of all fleshy-fruit types. In feeding trials, seeds of 11 species were retained on average for 309 min (±256 SD). Sampling radio-telemetry data randomly, that is, assuming foraging occurs at random times during the day, gives an estimated average dispersal distance of 239 m (±207 SD) for seeds consumed by C. casuarius. Approximately 4% of seeds were dispersed further than 1,000 m. However, observation of wild birds indicated that foraging and movement occur more frequently early and late in the day. Seeds consumed early in the day were estimated to receive dispersal distances 1.4 times the ‘random’ average estimate, while afternoon consumed seeds received estimated mean dispersal distances of 0.46 times the ‘random’ estimate. Sampling movement data according to the daily distribution of C. casuarius foraging gives an estimated mean dispersal distance of 337 m (±194 SD). Most animals’ behaviour has a non-random temporal distribution. Consequently such effects should be common and need to be incorporated into seed shadow estimation. Our results point to dispersal curves being an emergent property of the plant–disperser interaction rather than being a property of a plant or species.     

An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.

XRCC1, the human gene that fully corrects the Chinese hamster ovary DNA repair mutant EM9, encodes a protein involved in the rejoining of DNA single-strand breaks that arise following treatment with alkylating agents or ionizing radiation. In this study, a cDNA minigene encoding oligohistidine-tagged XRCC1 was constructed to facilitate affinity purification of the recombinant protein. This construct, designated pcD2EHX, fully corrected the EM9 phenotype of high sister chromatid exchange, indicating that the histidine tag was not detrimental to XRCC1 activity. Affinity chromatography of extract from EM9 cells transfected with pcD2EHX resulted in the copurification of histidine-tagged XRCC1 and DNA ligase III activity. Neither XRCC1 or DNA ligase III activity was purified during affinity chromatography of extract from EM9 cells transfected with pcD2EX, a cDNA minigene that encodes untagged XRCC1, or extract from wild-type AA8 or untransfected EM9 cells. The copurification of DNA ligase III activity with histidine-tagged XRCC1 suggests that the two proteins are present in the cell as a complex. Furthermore, DNA ligase III activity was present at lower levels in EM9 cells than in AA8 cells and was returned to normal levels in EM9 cells transfected with pcD2EHX or pcD2EX. These findings indicate that XRCC1 is required for normal levels of DNA ligase III activity, and they implicate a major role for this DNA ligase in DNA base excision repair in mammalian cells.     

Hydrothermal and oceanic pH conditions of possible relevance to the origin of life

Because of the continuous focusing of thermal and chemical energy, ancient submarine hot springs are contenders as sites for the origin of life. But it is generally assumed that these would be of the acid and high-temperature black smoker variety (Corlisset al., 1981). In fact today the greater part of the ocean circulates through off-ridge springs where it issues after modification at temperatures of around 40 °C or so but with the potential to reach 200 °C. Such offridge or ridge-flank springs remind us that there are other candidate sites for the origin of life. Although there is no firm indication of the pH of these off-ridge springs we have argued that the solutions are likely to be alkaline rather than acid.We test the feasibility of this idea using EQ geochemical water-rock interaction modelling codes (Wolery 1983) and find that for a range of possible initial chemistries of Hadean seawater, the pH of issuing solutions at around 200 °C is around one or more units alkaline. Such pH values hold for interaction with both basaltic and komatiitic crust. The robustness of this result suggests to us that alkaline submarine springs of moderate temperature, carrying many hundreds of ppm HS^– to the ocean basins, are also serious contenders as sites for the origin of life, particularly as Hadean seawater was probably slightly acid, with a dissolved iron concentration approaching 100 ppm. On mixing of these solutions, supersaturation, especially of iron sulphide, would lead to the precipitation of colloidal gels. In our view iron sulphide was the likely substance of, or contributor to, the first vesicle membranes which led to life, as the supply of organic molecules would have been limited in the Hadean. Such a membrane would have had catalytic properties, expansivity, and would have maintained the natural chemiosmotic gradient, a consequence of the acid ocean and the alkaline interior to the vesicles.     

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning

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The Drosophila retinoid X receptor homolog ultraspiracle functions in both female reproduction and eye morphogenesis.

Ultraspiracle (usp) encodes the Drosophila cognate of RXR, the human retinoid X receptor. To examine how RXR subfamily members function in development, we have undertaken a phenotypic analysis of usp mutants. usp is required at multiple stages of development for functions that occur in a wide variety of tissues. usp is required in the eye-antennal imaginal disc for normal eye morphogenesis and in the somatic and germline tissues of adult females for fertilization, eggshell morphogenesis and embryonic development. An unusual sunken eye phenotype with marked ventral-dorsal polarity appears to be caused by a lack of usp function in the imaginal disc cells that reside between the eye and antennal anlage. The usp functions include cell autonomous and non-cell autonomous components, suggesting that usp controls the production of factors important for both cell-cell communication and cellular differentiation. These usp signalling pathways have mechanistic parallels to steroid and retinoid action in developing vertebrate tissues.     

Multiple Mating,Paternity and Complex Fertilisation Patterns in the Chokka Squid Loligo reynaudii

Polyandry is widespread and influences patterns of sexual selection, with implications for sexual conflict over mating. Assessing sperm precedence patterns is a first step towards understanding sperm competition within a female and elucidating the roles of male- and female-controlled factors. In this study behavioural field data and genetic data were combined to investigate polyandry in the chokka squid Loligo reynaudii. Microsatellite DNA-based paternity analysis revealed multiple paternity to be the norm, with 79% of broods sired by at least two males. Genetic data also determined that the male who was guarding the female at the moment of sampling was a sire in 81% of the families tested, highlighting mate guarding as a successful male tactic with postcopulatory benefits linked to sperm deposition site giving privileged access to extruded egg strings. As females lay multiple eggs in capsules (egg strings) wherein their position is not altered during maturation it is possible to describe the spatial / temporal sequence of fertilisation / sperm precedence There were four different patterns of fertilisation found among the tested egg strings: 1) unique sire; 2) dominant sire, with one or more rare sires; 3) randomly mixed paternity (two or more sires); and 4) a distinct switch in paternity occurring along the egg string. The latter pattern cannot be explained by a random use of stored sperm, and suggests postcopulatory female sperm choice. Collectively the data indicate multiple levels of male- and female-controlled influences on sperm precedence, and highlights squid as interesting models to study the interplay between sexual and natural selection.