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MicroRNAs play an important role in the regulation of mRNA translation and have therapeutic potential in cancer and other diseases. To profile the landscape of microRNAs with significant cytotoxicity in the context of glioblastoma (GBM), we performed a high-throughput screen in adult and pediatric GBM cells using a synthetic oligonucleotide library representing all known human microRNAs. Bioinformatics analysis was used to refine this list and the top seven microRNAs were validated in a larger panel of GBM cells using state-of-the-art in vitro assays. The cytotoxic effect of our most relevant candidate was assessed in a preclinical model. Our screen identified ~100 significantly cytotoxic microRNAs with 70% concordance between cell lines. MicroRNA-1300 (miR-1300) was the most potent and robust candidate. We observed a striking binucleated phenotype in miR-1300 transfected cells due to cytokinesis failure followed by apoptosis. This was also observed in two stem-like patient-derived cultures. We identified the physiological role of miR-1300 as a regulator of endomitosis in megakaryocyte differentiation where blockade of cytokinesis is an essential step. In GBM cells, where miR-1300 is normally not expressed, the oncogene Epithelial Cell Transforming 2 (ECT2) was validated as a direct key target. ECT2 siRNA phenocopied the effects of miR-1300, and ECT2 overexpression led to rescue of miR-1300 induced binucleation. We showed that ectopic expression of miR-1300 led to decreased tumor growth in an orthotopic GBM model. Our screen provides a resource for the neuro-oncology community and identified miR-1300 as a novel regulator of endomitosis with translatable potential for therapeutic application.

The disruption to healthcare provision as a result of the COVID-19 pandemic has compelled us to streamline healthcare delivery. This has given us an opportunity to implement healthcare technology, reform inter-disciplinary collaboration and ultimately enhance patient care. We discuss some of the advances made by the foot and ankle department at our hospital. These innovations have broad applicability and will hopefully ignite discussion amoung a number of healthcare teams about improving the future care of their patients.

Objective:We investigated the frequencies and characteristics of out-of-hospital births in a 20-year period in California, where 1 of every 7 births in the United States occurs.Study Design:Birth certificate records of deliveries in California between 1991 and 2011 were analyzed. Out-of-hospital births were assessed by year, parity, gestational age and maternal race/ethnicity.Results:In the 20-year period there were 10 593,904 deliveries, of which 46 243 occurred out of hospital (0.44%). Out-of-hospital births decreased from 0.54 to 0.38% per year between 1991 and 2004, and increased from 0.41% in 2005 to 0.61% in 2011. In contrast, preterm out-of-hospital births declined from 7.2% in 2006 to 5.0% in 2011. The frequency of vaginal birth after cesarean in the out-of-hospital birth cohort increased from 1.2% (n=19) in 1996 to 4.2% (n=82) in 2011.Conclusion:California birth records from a 20-year period show an increase in out-of-hospital births from years 2005 to 2011, following a period of decline from 1991 to 2004.

•Explores the opinions of both parents and health care professionals within the same community about Cannabidiol as a treatment and the barriers.•This study finds that parents’ process for accessibility varies and struggles due to stigma, costs, resistance from the community, and lack of education on Cannabidiol (CBD).•Health care professionals advocate for more research and education while they worry about stigma within the medical community and professional and licensing risks with recommending treating children using Cannabidiol.•Parents and health care professionals are challenged with the resistance of support toward the use of medical cannabis from the political and professional community.•Lack of research regarding safety and efficacy guidelines of medical cannabis for children directly influences policy treatment and licensing risks for professionals.

AbstractProto-MPEX is a linear plasma device being used to study a novel RF source concept for the planned Material Plasma Exposure eXperiment (MPEX), which will address plasma-materials interaction (PMI) for nuclear fusion reactors. Plasmas are produced using a large diameter helicon source operating at a frequency of 13.56 MHz at power levels up to 120 kW. In recent experiments the helicon source has produced deuterium plasmas with densities up to ~6 × 1019 m–3measured at a location 2 m downstream from the antenna and 0.4 m from the target. Previous plasma production experiments on Proto-MPEX have generated lower density plasmas with hollow electron temperature profiles and target power deposition peaked far off axis. The latest experiments have produced flat Teprofiles with a large portion of the power deposited on the target near the axis. This and other evidence points to the excitation of a helicon mode in this case.

Objective:The association between obesity and spontaneous preterm births (sPTBs) has been shown to be influenced by obesity-attendant comorbidities. Our objective was to better understand the complex relationship of obesity and its attendant comorbidities with sPTBs.Study Design:A retrospective analysis utilizing maternally linked hospital and birth certificate records of 2 049 196 singleton California deliveries from 2007 to 2011. Adjusted relative risks (aRRs) for sPTBs were estimated using multivariate Poisson regression modeling.Results:Obese women had higher aRRs for sPTBs than their normal body mass index (BMI) controls. aRRs (95% confidence interval) increased with increasing BMI category: Obese I=1.10 (1.08 to 1.12); Obese II=1.15 (1.12 to 1.18); and Obese III=1.26 (1.22 to 1.30). When comparing only obese women without comorbidities to their normal BMI controls, aRRs reversed, that is, obese women had lower aRRs of sPTBs: Obese I=0.96 (0.94 to 0.98), Obese II=0.95 (0.91 to 0.98); and Obese III=0.98 (0.94 to 1.03). This same reversal of aRR direction was also observed among women with comorbidities: 0.92 (0.89 to 0.96); 0.89 (0.85 to 0.93); and 0.89 (0.85 to 0.93), respectively. Increasing BMI increased the aRRs for sPTBs among patients with gestational diabetes (P<0.05), while decreasing the risk among patients with chronic hypertension and pregnancy-related hypertensive disease (P<0.05).Conclusions:The obesity and preterm birth paradox is an example of what has been described as 'Simpson’s Paradox'. Unmeasured confounding factors mediated by comorbidities may explain the observed protective effect of obesity upon conditioning on the presence or absence of comorbidities and thus resolve the paradox.

Liver endothelial cell (LEC) damage is essential in the pathogenesis of ischemia–reperfusion injury (IRI) in transplant recipients. We analyzed the mechanism of LECresistance against IRIby using a novel recombinant soluble form of P selectin glycoprotein ligand 1, tandem P selectin glycoprotein ligand immunoglobulin (TSGL‐Ig), in a mouse model of hepatic cold preservation (4°C in University of Wisconsin solution for 20 h) and syngeneic orthotopic liver transplantation (OLT). Unlike controls, TSGL‐Ig protected orthotopic liver transplants against ischemia–reperfusion (IR) stress, shown by depressed serum alanine aminotransferase levels, well‐preserved hepatic architecture, and improved survival (42% vs. 92%). TSGL‐Ig suppressed neutrophil/macrophage sequestration and proinflammatory cytokine/chemokine programs in OLT. Treatment with TSGL‐Ig mitigated LECactivation (P and E selectin, VCAM‐1 and intercellular adhesion molecule 1 expression). In parallel in vitrostudies, TSGL‐Ig diminished cellular damage in H2O2‐stressed LECcultures (lactic acid dehydrogenase and alanine aminotransferase levels). Increased thioredoxin, glutamate‐cysteine ligase, NAD(P)H quinone dehydrogenase 1, and hypoxia‐inducible factor 1α expression, along with transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2), implied that TSGL‐Ig exerts antioxidant functions in IR‐stressed OLTand H2O2‐stressed LECs. Indeed, Nrf2‐deficient livers suffered fulminant IRIcompared with WTdespite concomitant TSGL‐Ig therapy. Thus, TSGL‐Ig is not only acting as a competitive antagonist blocking leukocyte migration into IR‐stressed liver, but it may also act directly as an agonist stimulating Nrf2‐mediated cytoprotection in LECs. This study supports the role of P selectin signaling in hepatic homeostasis in OLT, with broad implications for tissue damage conditions. TSGL‐Ig protection of liver endothelial cells mediated via antioxidant Nrf2 in hepatic ischemia–reperfusion injury highlights multifaceted functions of P‐selectin signaling beyond cell trafficking, of direct relevance in organ transplantation.

Aims.We present a comparison between independent computer codes, modeling the physics and chemistry of interstellar photon dominated regions (PDRs). Our goal was to understand the mutual differences in the PDR codes and their effects on the physical and chemical structure of the model clouds, and to converge the output of different codes to a common solution.

Objective:: To quantify the importance of successful endotracheal intubation on the first attempt among extremely low birth weight (ELBW) infants who require resuscitation after delivery. Study Design:: A retrospective chart review was conducted for all ELBW infants ?1000?g born between January 2007 and May 2014 at a level IV neonatal intensive care unit. Infants were included if intubation was attempted during the first 5?min of life or if intubation was attempted during the first 10?min of life with heart rate &lt;100. The primary outcome was death or neurodevelopmental impairment. The association between successful intubation on the first attempt and the primary outcome was assessed using multivariable logistic regression with adjustment for birth weight, gestational age, gender and antenatal steroids. Results:: The study sample included 88 ELBW infants. Forty percent were intubated on the first attempt and 60% required multiple intubation attempts. Death or neurodevelopmental impairment occurred in 29% of infants intubated on the first attempt, compared with 53% of infants that required multiple attempts, adjusted odds ratio 0.4 (95% confidence interval 0.1 to 1.0), P&lt;0.05. Conclusion:: Successful intubation on the first attempt is associated with improved neurodevelopmental outcomes among ELBW infants. This study confirms the importance of rapid establishment of a stable airway in ELBW infants requiring resuscitation after birth and has implications for personnel selection and role assignment in the delivery room.

Models to predict the fate of gaseous radionuclides have received considerable attention in the literature. They vary considerably in their complexity from simple models with little attempt to reflect processes within the system to those with a high level of mechanistic complexity. The following paper describes an approach that is a compromise between simplicity and realism. In the proposed model deposition is treated traditionally as the multiple of the air concentration, deposition velocity and exposure time but the subsequent allocation of radioactivity to different plant parts is determined by the growth rate of individual plant components relative to the total growth rate of the plant. The construction of the model is described along with its validation against independent data sets for the allocation of 35S and 14C in cabbage and bean following deposition in the form of CO35S and, 14CO2at a number of discrete points in the growth season.

A series of laboratory-based soil column studies has been carried out to determine the comparative behaviour of the radioactive halogens 36Cl and 125I (as a surrogate for 129I) in the soil-plant system. Physical migration of 36Cl in the soil appears to be unretarded due to its presence predominantly in the chloride form. This lead to substantial accumulation of 36Cl at the soil surface in a column experiment in which the net flux of water was upwards. Physical migration of 125I in soils appears to be relatively rapid at low oxidation-reduction potentials, but is substantially retarded under more oxic soil conditions. This lead to accumulation of 125I in the zone of transition between anoxic and oxic zones in the soil. Gel filtration chromatography confirmed that the predominant chemical form of 36Cl in the soil is the chloride anion. Conversely, 125I showed a strong tendency to associate with both high and low molecular weight fractions of soil humic substances, though its attachment to the low molecular weight fraction appears to be more specific than to the high molecular weight fraction. Soil-plant transfer was measured for both 36Cl and 125I in rye grass swards in undisturbed soil columns. Biological assimilation of 36Cl was particularly significant, with more than 50 % of the total 36Cl activity in the soil being taken up by the grass sward after three weeks' growth. Uptake of 125I by grass swards was less spectacular, though still resulted in approximately 1 % of the total soil 125I activity being assimilated even though the standing biomass of the grass sward was low.

The ability to predict the consequences of an accidental release of radioactive nuclides relies mainly on the level of understanding of the mechanisms involved in radioactive nuclides interactions with different components of agricultural and natural ecosystems and their formalisation into predictive models. Numerous studies and databases about contaminated agricultural and natural areas have been obtained but their use to enhance our prediction ability has been largely limited by their unresolved variability. Such variability seems to stem from an incomplete knowledge about radioactive nuclide interactions with the soil matrix, soil moisture, biological elements in the soil and additional pollutants, which may be found in such soils. In this project, we investigate mainly the role of the biological elements (plants, mycorrhiza, microbes) in: radioactive nuclide sorption/desorption in soils and radioactive nuclide uptake/release by plants. Because of the importance of the chemical nature of the involved radioactive nuclides, we will follow the bioavailability of three radioactive nuclides : caesium, strontium, and technetium. The role of additional non-radioactive pollutants will also be scrutinised as they may interfere with the mechanisms governing radioactive nuclide transfer to plants. Knowledge acquired from the experiments will be incorporated into two mechanistic models BIOPHAST and BIORUR specifically modelling radioactive nuclide sorption/desorption from soil matrices and radioactive nuclide uptake by/release from plants. These mechanistic models will be incorporated into assessment models to enhance their prediction ability. One expects to extract from these experiments scientific bases for the development of bioremediation methods of radioactive nuclide-contaminated soils.

AbstractThis paper brings together the work of the GI Solvency II Technical Provisions working party. The working party was formed in 2009 for the primary purpose of raising awareness of Solvency II and the impact it would have on the work that reserving actuaries do. Over the years, the working party’s focus has shifted to exploring and promoting discussion of the many practical issues raised by the requirements and to promoting best practice. To this end, we have developed, presented and discussed many of the ideas contained in this paper at events and forums. However, the size of the subject means that at no one event have we managed to cover all of the areas that the reserving actuary needs to be aware of. This paper brings together our thinking in one place for the first time. We hope experienced practitioners will find it thought provoking, and a useful reference tool. For new practitioners, we hope it helps to get you up-to-speed quickly. Good luck!

Planning for the disposal of spent nuclear fuel is at an advanced stage in several nations around the world. Licensing of the disposal facility requires correspondingly detailed assessment of the future performance of the facility. With increased site-specific detail available to the assessment, local characteristics play an increasingly important role in determining the potential radiological risk posed by releases to the biosphere. In this paper we go beyond existing reference biospheremodels and investigate the potential for specific accumulation mechanisms. The implications for the modelling carried out in long timescale performance assessment are discussed.

Reaching out to other doctors and specialists for referrals can benefi t your patients and your practice. [ABSTRACT FROM AUTHOR]

Practical strategies for the structural elucidation of small organic molecules are described for typical organic chemists. The analysis of an unknown is divided into three stages. First, structural connectivity is deduced from through-bond correlation experiments. Next, the relative stereochemistry is determined from NOE correlations and coupling constants (both proton–proton and proton–carbon). Finally, the proposed structure is verified by a careful inspection of all of the observed data. Tactics for the management of overlapping peaks, low sample concentrations, and high molecular weights are also described. This approach is illustrated by the step-by-step analyses of a simple test compound, menthol, and a complex polycyclic natural product, salvinorin A. Detailed procedures and sample data for menthol are provided as a practical tutorial. This will enable organic chemists to elucidate a wide range of complex structures by using modern NMR spectroscopic experiments.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Magnification of anteroposterior radiographs of the pelvis is variable. To improve the accuracy of templating, reliable and radiographer-friendly methods of scaling are necessary. We assessed two methods of scaling digital radiographs of the pelvis: placing a coin of known diameter in the plane of interest between the patient’s thighs, and using a caliper to measure the bony width of the pelvis. A total of 39 patients who had recently undergone hemiarthroplasty of the hip or total hip replacement were enrolled in the study. The accuracy of the methods was assessed by comparing the actual diameter of the head of the prosthesis with the measured on-screen value. The coin method was within a mean of 1.12% (0% to 2.38%) of the actual measurement, the caliper group within 6.99% (0% to 16.67%). The coin method was significantly more accurate (p < 0.001). It was also reliable and radiographer friendly. We recommend it as the method of choice for scaling radiographs of the pelvis before hip surgery.

Harmful algal blooms (HABs) have increased in abundance and severity in recent decades. Whereas the implications for human impacts and intoxication resulting from blooms have been extensively studied, the ecological implications of these microalgae are less well understood. Many HAB species produce biologically active, secondary metabolites and the fate of these toxins through the foodweb is generally not well understood unless it culminates in extensive fish mortalities or human poisonings. This review focusses on one HAB species, the cyanobacterium Lyngbya majuscula, and presents a hypothetical role for its involvement in fibropapillomatosis (FP), a neoplastic disease of marine turtles. FP is expressed as benign tumours that grow both internally and externally on marine turtles, preventing vision, movement and organ function. The aetiology of FP is currently not conclusively understood, but virus material has been associated with tumours and previous studies have suggested a role for naturally produced tumour promoters. In this review, we present a hypothesis regarding the involvement of L. majuscula in FP, either through direct intoxication and action of tumour-promoting compounds or indirectly by causing seagrass loss and compromised immune function, thus leaving the turtles more susceptible to disease.

The ability to predict the consequences of an accidental release of radionuclides relies mainly on the level of understanding of the mechanisms involved in radionuclides interactions with different components of agricultural and natural ecosystems and their formalisation into predictive models. Numerous studies and databases about contaminated agricultural and natural areas have been obtained but their use to enhance our prediction ability has been largely limited by their unresolved variability. Such variability seems to stem from incomplete knowledge about radionuclide interactions with the soil matrix, soil moisture, biological elements in the soil and additional pollutants, which may be found in such soils. In this project, we investigated mainly the role of the biological elements (plants, mycorrhiza, microbes) in: radionuclide sorption/desorption in soils and radionuclide uptake/release by plants. Because of their chemical nature importance, the bioavailability of three radionuclides: caesium, strontium, and technetium have been followed. The role of one additional non-radioactive pollutant (copper) has been scrutinised. Role of microorganisms (Kd for caesium and strontium in organic soils is much greater in the presence of microorganisms than in their absence), plant physiology (changes in plant physiology affect radionuclide uptake by plants), the presence of mycorrhizal fungi (interferes with the uptake of radionuclides by plants), have been demonstrated. Knowledge acquired from these experiments has been incorporated into two mechanistic models CHEMFAST and BIORUR specifically modelling radionuclide sorption/desorption from soil matrices and radionuclide uptake by/release from plants. These mechanistic models have been incorporated into an assessment model to enhance its prediction ability.

Vertical distributions of 36Cl and 99Tc are presented from deep and shallow lysimeters above artificially controlled water tables for a 4‐yr experiment from 1990 to 1993. Activity concentration profiles were all measured in late summer when a winter wheat (Triticum aestivumL. cv. Pastiche) crop was harvested. After harvest, activity concentrations in different organs of the crop were determined and crop uptake quantified as both an inventory ratio (IR) and a transfer factor (TFw), weighted to account for differential root and radionuclide distributions within the soil profile. Vertical distributions of radionuclides, crop roots within the soil, and IR and TFwvalues were each subjected to analysis of variance to estimate the individual and combined effects of soil depth and the year of the experiment on the results obtained. Chlorine‐36 and 99Tc exhibited highly significant variations in activity concentrations with soil depth and from year to year, indicating considerable physical mobility of both radionuclides. Soil‐to‐plant transfer was also high for both radionuclides compared with data obtained for gamma‐emitting radionuclides. The IR values indicated that up to 40% of 36Cl was incorporated in the crop's tissues at harvest, compared with a maximum of less than 1% for the less mobile gamma‐emitting radionuclides. On the basis of the TFwvalues determined, 36Cl uptake by winter wheat exceeded 99Tc uptake, indicating that 36Cl is highly bioavailable. Factors controlling the migration and bioavailability of both 36Cl and 99Tc in soils are discussed.

Genetic algorithms are applied to the design optimization of a lightguide. Physically impossible offspring generated by the genetic algorithm evolution are removed by a simple logical test before further iterations. The performance of the lightguide and the evolution of the design are measured by a single criterion combining both uniformity of illumination and brightness. The process produces a nonintuitive solution, and experimental results match the theoretical predictions and show an improvement in performance of the final design. © 2004 Society of Photo-Optical Instrumentation Engineers.

This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P< 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P> 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.

The reaction of gallium trichloride and methanol under atmospheric pressure chemical vapor deposition conditions leads to the production of gallium oxide thin films on a variety of substrates. Scanning electron microscopy (SEM) indicated that an island growth mechanism predominated. X-ray photoelectron spectroscopy (XPS) revealed binding energy shifts of 530.6 eV for O 1s and 20.3 eV for Ga 3d. The films were X-ray amorphous. Energy-dispersive X-ray analysis (EDXA) and electron probe microanalysis (EPMA) gave coherent elemental compositions, indicating that a single phase Ga2O3 was made, with negligible impurity levels. The films showed little optical reflectance (~10%) and 65−75% total transmission from 400 to 800 nm. Gas-sensing experiments indicated that the films responded best to a reducing gas at 450 °C.

Androgens are essential for testicular descent in eutherian mammals, but little is known about its hormonal control in marsupials. This study reports the effects of daily treatment with the anti-androgen flutamide (10 mg kg(-1)) from day 9 to day 75 after birth on the descent of the testis and inguinal closure in tammar wallabies. By day 75 after birth, the testes of control males had descended and the prostate gland was well developed. The testes of all flutamide-treated males had passed through the inguinal canal and were situated in the base of the scrotum. Three of the nine flutamide-treated males had unilateral inguinal hernias. The size of the inguinal canal, regardless of whether a hernia was present, was significantly wider than that of control males. Development of the prostate gland was significantly inhibited. By day 75 after birth, the phallus was significantly longer in control males than in females, whereas the phallus of flutamide-treated males was similar to that of control females. In flutamide-treated males, the lumbar 1 dorsal root ganglia was feminized and significantly fewer cell bodies expressed calcitonin gene- related peptide. As the anti-androgen treatment resulted in a reduction in the number of calcitonin gene-related peptide-positive cell bodies in the dorsal root ganglion supplying the genitofemoral nerve, the process of inguinal closure in tammar wallabies may be mediated by calcitonin gene-related peptide via the genitofemoral nerve, as indicated in humans. Flutamide treatment inhibited development of the prostate gland and phallus, which are both androgen-dependent structures, but it did not affect the normal descent of the testis, indicating that testicular descent can proceed when the action of androgens is blocked.

To investigate mechanisms predisposing to alcoholic brain damage, thiamine (vitamin B1), riboflavin (vitamin B2) and pyridoxine (vitamin B6) status was compared in persistent alcohol misusers (PAM) admitted for detoxification without evidence of significant brain damage, in alcoholics known to have severe chronic brain damage (BDAM), and in age, gender and ethnicity matched controls. Thus, activities of thiamine-dependent transketolase (ETK), riboflavin-dependent glutathione reductase, and pyridoxine-dependent aspartate amino transferase were assayed, together with the enzyme activities following in vitroaddition of the appropriate co-factor. Twenty per cent of the PAM group had an abnormally low ETK activity and an abnormally high activation ratio, while 45 were abnormal in either one or both parameters. An additional 10 of the PAM group had an abnormally high activation ratio but normal ETK activity, as did 30 of the BDAM group. These subgroups of alcohol misusers may have increased requirements for thiamine secondary to an abnormality of the transketolase protein that may predispose such patients to alcoholic brain damage. There was no evidence of riboflavin or pyridoxine deficiency in either of the patient groups. We conclude that thiamine deficiency was commonly present in the alcoholic patients, and that a subgroup of patients may be predisposed to more severe brain damage as a consequence of abnormalities in the transketolase protein.

Abstract. A genetic locus that is adjacent to the gene encoding the small acid-soluble protein SASP C-4 of Bacillus megaterium has been identified. This locus, designated fru, contains a β-fructosidase gene (fruA), a gene encoding a hydrophobic protein that is closely related to non-PTS sugar permeases of the proton symport type (fruP), and a gene coding for a transcriptional regulator of the LacI/GalR family (fruR). The FruA protein can hydrolyze sucrose and raffinose, but not maltose, isomaltose, trehalose, melibiose or lactose. The transcription initiation site of fruP has been mapped and the fruP promoter identified. Gel mobility shift assays showed that the FruR protein can bind specifically to a DNA fragment containing the fruP promoter region. DNase I footprinting analysis has defined the FruR binding site. Disruption of fruR led to high-level constitutive expression of fruPA, but had no effect on expression from the fruR promoter itself, indicating that FruR acts as a repressor of fruPA expression, but does not autoregulate its own synthesis. Interestingly, expression of fruPA in B. megaterium was not induced by sucrose, raffinose, fructose or inulin, whereas the constitutive expression of fruPA in a fruR mutant was repressed by both glucose and sucrose. Possible physiological implications of these findings are discussed.

This study reports the effect of oestrogen treatment on the development of the genital ducts, prostate gland, testicular descent and inguinal canal closure in male tammar wallaby young treated with oestrogen over four time spans during the first 25 days of pouch life (days 0-10, 10-15, 15-25 and 0-25) and sampled at day 50. In control males, the Mullerian ducts had regressed and the Wolffian ducts had developed into the vas deferens and epididymis. The prostate gland had formed epithelial buds extending from the ventral, lateral and posterior walls of the urethra. The testes were in the neck of the scrotum and the gubernaculum and processus vaginalis were present at the base of the scrotum. In most males treated with oestradiol from day 0 to day 25, the testes had failed to descend by day 50. The gubernaculae were long and thin. The retained Mullerian ducts formed a lateral vaginal expansion like that of normal day 50 females. The Wolffian ducts of the males treated on days 0-25 were regressed, but were present in males in the other three treatment groups. The prostate glands were hyperplastic and epithelial budding was highly invasive. Some treated males from the day 10-25 and 0-25 groups had inguinal hernias. These results demonstrate that oestrogen treatment has profound effects on the development of the internal genitalia of a male marsupial, preventing inguinal closure and interfering with testicular descent. Therefore, the tammar wallaby may provide a useful experimental model animal in which to investigate the hormonal control of testicular migration and closure of the inguinal canal.

Femtosecond transient absorption spectroscopy is used to study the triplet−triplet annihilation (TTA) interaction between the metal-to-ligand charge-transfer (MLCT) excited states of Ru(II) polypyridyl complexes bound to a polystyrene backbone. The polymer chains have, on average, 20 repeat units, each functionalized with a transition metal complex. Spectroscopic experiments are performed on assemblies dissolved in acetonitrile at room temperature. The time-resolved spectra show kinetics that depend on the intensity of the excitation laser. These effects are attributed to the interaction between multiple excited states formed on a single chain. Fast and slow (intensity-dependent) kinetic components are observed. The fast (3 ps) component is assigned to the TTA of MLCT excited states formed at adjacent sites within the assembly, while the slow component is attributed to TTA between excited states that must undergo energy migration prior to annihilation. Femtosecond experiments are also performed on Ru(bpy)3²⁺ (bpy = 2,2‘-bipyridine) and a mixed-ligand Ru(II) complex that serves as a reference system for the polymer.