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Highlights: [•] We directly measure the isotopic composition of NEE in a forest by eddy covariance. [•] Precision is limited both by instrument noise and by horizontal heterogeneity. [•] Precision is sufficient to partition NEE into photosynthesis and respiration. [•] The ‘EC/flask’ indirect flux measurement method can be biased by 2‰. [•] Laser spectrometer accuracy is on par with isotope ratio mass spectrometry. [ABSTRACT FROM AUTHOR]

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We report on the design and laboratory performance of a portable infrared absorption spectrometer for the measurement of the isotopic ratio 13C:12C in CO2. The design relies on optical feedback cavity-enhanced absorption spectroscopy in the 2 μm spectral region to achieve optimal performance at ambient CO2 concentrations. The prototype instrument measures δ13C, relative to a standard calibration bottle, with a precision of ±0.7‰ for a 20-s integration time and with an automatic recalibration every 6 min. The absolute accuracy obtained is 0.9‰. The principal performance limitations are discussed along with improvements currently being implemented for the second generation instrument. [ABSTRACT FROM AUTHOR]

We report on the design and laboratory performance of a portable infrared absorption spectrometer for the measurement of the isotopic ratio 13C:12C in CO2. The design relies on optical feedback cavity-enhanced absorption spectroscopy in the 2 μm spectral region to achieve optimal performance at ambient CO2 concentrations. The prototype instrument measures δ13C, relative to a standard calibration bottle, with a precision of ±0.7‰ for a 20-s integration time and with an automatic recalibration every 6 min. The absolute accuracy obtained is 0.9‰. The principal performance limitations are discussed along with improvements currently being implemented for the second generation instrument. [ABSTRACT FROM AUTHOR]

The 0310 ← 0110 parallel Q branch of N2O has been studied at 297 K and over the pressure range 1–130 torr. Absorption spectra were recorded using a high resolution (1.5 MHz or 5 × 10-5 cm-1) and high signal-to-noise (>3500:1) mid-infrared spectrometer based on difference-frequency infrared generation in AgGaS2. In the low-pressure range (1–11 torr) we obtained accurate values for the line strengths, the broadening coefficients, the weak mixing coefficients, and the overall shifting of the branch. The medium pressure results, ranging from 23 to 130 torr, were analyzed by treating the band as a whole, using a relaxation matrix formalism, based on an energy gap scaling law. We find, effectively, that only 36% of the rotationally inelastic collisions are associated with Q branch mixing, the rest presumably being associated with Q–P and Q–R mixing in the same vibrational band. The pressure shifting coefficient of the 0310 ← 0110 Q branch as a whole was also determined and found to be 5.8 × 10-3 cm-1/atm towards lower frequencies. [Copyright &y& Elsevier]

An overview of the binary collision impact theory of spectral line shapes has been given to provide a unified statistical mechanical approach to line-shape theory, laser theory, nonlinear optics, and transport phenomena in dilute gases. The computation of spectral line profiles corresponding to those obtained from ultra-high-resolution spectral line-shape measurements requires numerical ab initio calculation of scattering amplitudes directly from the underlying dynamics of collisions between radiatively active molecules and their perturbers. The Wigner distribution function-density matrix is utilized to describe the kinetic theory of spectral line shapes and to discuss the various collisional processes that contribute to the kernel of kinetic equations. The influence of features of the potential energy surface on spectral parameters is also discussed, and the importance of comparing experimental line profiles directly with numerically computed line shapes obtained from reliable interaction potentials is emphasized. This contrasts sharply with the universal practice of comparing experimental line widths and shifts using some average or approximate theoretical scattering cross-sections and it contrasts sharply with fitting experimental profiles to some convenient analytical line-shape model; hence the phrase 'a paradigm shift' in the title of this work. [ABSTRACT FROM AUTHOR]

Territorial Differential Meta-Evolution (TDME) is an efficient, versatile, and reliable algorithm for seeking all the global or desirable local optima of a multivariable function. It employs a progressive niching mechanism to optimize even challenging, highdimensional functions with multiple global optima and misleading local optima. This article introduces TDME and uses standard and novel benchmark problems to quantify its advantages over HillVallEA, which is the best-performing algorithm on the standard benchmark suite that has been used by all major multimodal optimization competitions since 2013. TDME matches HillVallEA on that benchmark suite and categorically outperforms it on a more comprehensive suite that better reflects the potential diversity of optimization problems. TDME achieves that performance without any problem-specific parameter tuning., (© 2023 Massachusetts Institute of Technology.)

Rationale: The simultaneous analysis of the three stable isotopes of oxygen-triple oxygen isotope analysis-has become an important analytical technique in natural sciences. Determination of the abundance of the rare 17 O isotope in CO 2 gas using magnetic sector isotope ratio mass spectrometry is complicated by the isobaric interference of 17 O by 13 C ( 13 C 16 O 16 O and 12 C 16 O 17 O, both have mass 45 amu). A number of analytical techniques have been used to measure the 17 O/ 16 O ratio of CO 2 gas. They either are time consuming and technically challenging or have limited precision. A rapid and precise alternative to the available analytical methods is desirable., Methods: We present the results of triple oxygen isotope analyses using an Aerodyne tunable infrared laser direct absorption spectroscopy (TILDAS) CO 2 analyzer configured for 16 O, 17 O, and 18 O combined with a custom gas inlet system. We evaluate the sensitivity of our results to a number of parameters. CO 2 samples with a wide range of δ 18 O values (from -9.28‰ to 39.56‰) were measured and compared to results using the well-established fluorination-gas source mass spectrometry method., Results: The TILDAS system has a precision (standard error, 2σ) of better than ±0.03‰ for δ 18 O and ±10 per meg for Δ' 17 O values, equivalent to the precision of previous analytical methods. Samples as small as 3 μmol CO 2 (equivalent to 300 μg CaCO 3 ) can be analyzed with a total analysis time of ~30 min., Conclusions: We have successfully developed an analytical technique for the simultaneous determination of the δ 17 O and δ 18 O values of CO 2 gas. The precision is equal to or better than that of existing techniques, with no additional chemical treatments required. Analysis time is rapid, and the system is easily automated so that large numbers of samples can be analyzed with minimal effort., (© 2022 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Objectives: This study aimed to compare assessment methods to determine adverse drug reactions (ADRs) at nonelective hospital admission in pediatric patients, to investigate the interrater reliability of assessment methods in pediatric care, and to analyze symptoms related to ADRs and (suicidal) drug intoxications., Methods: For 1 year, the medical records of nonelective patients admitted to a university pediatric department were evaluated for potential ADRs using 4 assessments methods by 1 experienced rater. Krippendorff α was calculated from a sample of 14 patients evaluated by 4 experienced raters to determine interrater reliability., Results: In 1831 nonelective hospital admissions, 63.4% (1161 of 1831) of patients had received at least one drug before admission. We found a potential causal relationship between drugs and symptoms documented at admission and thus potential ADRs according to Naranjo in 23.3% (271 of 1161) of those patients, World Health Organization - Uppsala Monitoring Centre (WHO-UMC) in 22.5% (261 of 1161), Koh in 21.7% (252 of 1161), and Begaud in 16.5% (192 of 1161). The probability rating of the potential causal relationships varied considerably between the methods (Naranjo-Begaud, P < 0.01; Naranjo-Koh, P < 0.001; Koh-Begaud, P < 0.01; Begaud-WHO-UMC, P < 0.01). Acceptable interrater reliability (α ≥ 0.667) was only obtained for WHO-UMC (α = 0.7092). The most frequently identified definite ADR was sedation in 1.5% of all nonelective patients with medication before hospital admission. In 1.2% (22 of 1831) of all nonelective admissions, we found drug intoxications with suicidal intent., Conclusions: The assessment methods showed a high variability in the determination of a potential causal relationship between drug and documented symptom, in the classification of the probability of ADRs, and suboptimal interrater reliability. Thus, their feasibility in pediatric patients is limited., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Combining amphiphilic block copolymers and phospholipids opens new opportunities for the preparation of artificial membranes. The chemical versatility and mechanical robustness of polymers together with the fluidity and biocompatibility of lipids afford hybrid membranes with unique properties that are of great interest in the field of bioengineering. Owing to its straightforwardness, the solvent-assisted method (SA) is particularly attractive for obtaining solid-supported membranes. While the SA method was first developed for lipids and very recently extended to amphiphilic block copolymers, its potential to develop hybrid membranes has not yet been explored. Here, we tailor the SA method to prepare solid-supported polymer-lipid hybrid membranes by combining a small library of amphiphilic diblock copolymers poly(dimethyl siloxane)-poly(2-methyl-2-oxazoline) and poly(butylene oxide)- block -poly(glycidol) with phospholipids commonly found in cell membranes including 1,2-dihexadecanoyl- sn -glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoethanolamine, sphingomyelin, and 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine- N -(glutaryl). The optimization of the conditions under which the SA method was applied allowed for the formation of hybrid polymer-lipid solid-supported membranes. The real-time formation and morphology of these hybrid membranes were evaluated using a combination of quartz crystal microbalance and atomic force microscopy. Depending on the type of polymer-lipid combination, significant differences in membrane coverage, formation of domains, and quality of membranes were obtained. The use of the SA method for a rapid and controlled formation of solid-supported hybrid membranes provides the basis for developing customized artificial hybrid membranes.

Droughts in a warming climate have become more common and more extreme, making understanding forest responses to water stress increasingly pressing. Analysis of water stress in trees has long focused on water potential in xylem and leaves, which influences stomatal closure and water flow through the soil-plant-atmosphere continuum. At the same time, changes of vegetation water content (VWC) are linked to a range of tree responses, including fluxes of water and carbon, mortality, flammability, and more. Unlike water potential, which requires demanding in situ measurements, VWC can be retrieved from remote sensing measurements, particularly at microwave frequencies using radar and radiometry. Here, we highlight key frontiers through which VWC has the potential to significantly increase our understanding of forest responses to water stress. To validate remote sensing observations of VWC at landscape scale and to better relate them to data assimilation model parameters, we introduce an ecosystem-scale analog of the pressure-volume curve, the non-linear relationship between average leaf or branch water potential and water content commonly used in plant hydraulics. The sources of variability in these ecosystem-scale pressure-volume curves and their relationship to forest response to water stress are discussed. We further show to what extent diel, seasonal, and decadal dynamics of VWC reflect variations in different processes relating the tree response to water stress. VWC can also be used for inferring belowground conditions-which are difficult to impossible to observe directly. Lastly, we discuss how a dedicated geostationary spaceborne observational system for VWC, when combined with existing datasets, can capture diel and seasonal water dynamics to advance the science and applications of global forest vulnerability to future droughts., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The introduction of chirality into aqueous self-assemblies by employing isotactic block copolymers (BCPs) is an emerging field of interest as it promises special membrane properties of polymersomes not accessible by atactic BCPs. However, isotactic BCPs typically exhibit crystalline behaviour, inducing high membrane stiffness and limiting their applicability in systems involving membrane proteins or sensitive cargo. In this study, an isotactic yet fully amorphous BCP is introduced which overcomes these limitations. Three BCPs composed of poly(butylene oxide)- block -poly(glycidol) (PBO- b -PG), differing solely in their tacticities ( R / S , R and S ), were synthesised and characterised regarding their structural, optical and thermal properties. Their self-assembly into homogenous phases of nanoscopic polymersomes (referred to as small unilamellar vesicles, SUVs) was analysed, revealing stability differences between SUVs composed of the different BCPs. Additionally, microscopic giant unilamellar vesicles (GUVs) were prepared by double emulsion microfluidics. Only the atactic BCP formed GUVs which were stable over several hours, whereas GUVs composed of isotactic BCPs ruptured within several minutes after formation. The ability of atactic PBO- b -PG to form microreactors was elucidated by reconstituting the membrane protein OmpF in the GUV membrane by microfluidics and performing an enzyme reaction inside its lumen. The system presented here serves as platform to design versatile vesicles with flexible membranes composed of atactic or isotactic BCPs. Hence, they allow for the introduction of chirality into nano- or microreactors which is a yet unstudied field and could enable special biotechonological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here, we introduce an artificial bioluminescent nanocompartment based on the encapsulation of light-producing enzymes, luciferases, inside polymersomes. We exploit nanocompartmentalization to enhance luciferase stability in a cellular environment but also to positively modulate enzyme kinetics to achieve a long-lasting glow type signal. These features pave the way for expanding bioluminescence to nanotechnology-based applications.

Aqueous self-assembly of amphiphilic block copolymers is studied extensively for biomedical applications like drug delivery and nanoreactors. The commonly used hydrophilic block poly(ethylene oxide) (PEO), however, suffers from several drawbacks. As a potent alternative, poly(glycidol) (PG) has gained increasing interest, benefiting from its easy synthesis, high biocompatibility and flexibility as well as enhanced functionality compared to PEO. In this study, we present a quick and well-controlled synthesis of poly(butylene oxide)- block -poly(glycidol) (PBO- b -PG) amphiphilic diblock copolymers together with a straight-forward self-assembly protocol. Depending on the hydrophilic mass fraction of the copolymer, nanoscopic micelles, worms and polymersomes were formed as well as microscopic giant unilamellar vesicles. The particles were analysed regarding their size and shape, using dynamic and static light scattering, TEM and Cryo-TEM imaging as well as confocal laser scanning microscopy. We have discovered a strong dependence of the formed morphology on the self-assembly method and show that only solvent exchange leads to the formation of homogenous phases. Thus, a variety of different structures can be obtained from a highly flexible copolymer, justifying a potential use in biomedical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Controllable attachment of proteins to material surfaces is very attractive for many applications including biosensors, bioengineered scaffolds or drug screening. Especially, redox proteins have received considerable attention as a model system not only to understand the mechanism of electron transfer in biological systems, but also the development of novel biosensors. However, current research attempts suffer from denaturation of the protein after its attachment to solid substrates. Here, we present how lipid, polymer and hybrid membranes based on mixtures of lipids and copolymers on a solid support provide a more favorable environment to drive selective and functional attachment of a model redox protein, cytochrome  c (cyt c ). Polymer membranes provided chemical versatility to support covalent attachment of cyt c , whereas lipid membranes provided flexibility and biocompatibility to support insertion of cyt c through its hydrophobic part. Hybrid membranes combine the most promising characteristics of both lipids and polymers and allowed attachment of cyt  c with both covalent attachment and insertion driven by hydrophobic interactions. We then investigated the effect of different attachment strategies on the accessibility and peroxidase-like activity of cyt c , in the presence of different membranes. The real-time combination of cyt c with the planar membranes was investigated by quartz crystal microbalance with dissipation. It was possible to selectively drive the insertion of cyt c into a specific lipid domain of hybrid membranes. In addition, protein accessibility and its functionality were dependent on the specificity of the combination strategy: covalent conjugation of cyt c to polymer and hybrid membranes promoted higher accessibility and supported higher peroxidase-like activity. Taking together, the combination of biomolecules with planar membranes can be modulated in such a way to improve the accessibility of the biomolecules and their resulting functionality for the development of efficient "active surfaces".

The recent development of polymerization-induced self-assembly (PISA) has facilitated the rational synthesis of a range of diblock copolymer worms, which hitherto could only be prepared via traditional post-polymerization processing in dilute solution. Herein we explore a new synthetic route to aqueous dispersions of cationic disulfide-functionalized worm gels. This is achieved via the PISA synthesis of poly[(glycerol monomethacrylate- stat -glycidyl methacrylate)]- block -poly(2-hydroxypropyl methacrylate) (P(GMA- stat -GlyMA)-PHPMA) block copolymer worms via reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of HPMA. A water-soluble reagent, cystamine, is then reacted with the pendent epoxy groups located within the P(GMA- stat -GlyMA) stabilizer chains to introduce disulfide functionality, while simultaneously conferring cationic character via formation of secondary amine groups. Moreover, systematic variation of the cystamine/epoxy molar ratio enables either chemically cross-linked worm gels or physical (linear) primary amine-functionalized disulfide-based worm gels to be obtained. These new worm gels were characterized using gel permeation chromatography, 1 H NMR spectroscopy, transmission electron microscopy, dynamic light scattering, aqueous electrophoresis and rheology. In principle, such hydrogels may offer enhanced mucoadhesive properties.

1. The pharmacokinetics and metabolism of lumiracoxib in male C57bl/6J mice were investigated following a single oral dose of 10 mg/kg. 2. Lumiracoxib achieved peak observed concentrations in the blood of 1.26 + 0.51 μg/mL 0.5 h (0.5-1.0) post-dose with an AUC inf of 3.48 + 1.09 μg h/mL. Concentrations of lumiracoxib then declined with a terminal half-life of 1.54 + 0.31 h. 3. Metabolic profiling showed only the presence of unchanged lumiracoxib in blood by 24 h, while urine, bile and faecal extracts contained, in addition to the unchanged parent drug, large amounts of hydroxylated and conjugated metabolites. 4. No evidence was obtained in the mouse for the production of the downstream products of glutathione conjugation such as mercapturates, suggesting that the metabolism of the drug via quinone-imine generating pathways is not a major route of biotransformation in this species. Acyl glucuronidation appeared absent or a very minor route. 5. While there was significant overlap with reported human metabolites, a number of unique mouse metabolites were detected, particularly taurine conjugates of lumiracoxib and its oxidative metabolites.

Gross ecosystem productivity (GEP) in tropical forests varies both with the environment and with biotic changes in photosynthetic infrastructure, but our understanding of the relative effects of these factors across timescales is limited. Here, we used a statistical model to partition the variability of seven years of eddy covariance-derived GEP in a central Amazon evergreen forest into two main causes: variation in environmental drivers (solar radiation, diffuse light fraction, and vapor pressure deficit) that interact with model parameters that govern photosynthesis and biotic variation in canopy photosynthetic light-use efficiency associated with changes in the parameters themselves. Our fitted model was able to explain most of the variability in GEP at hourly (R 2  = 0.77) to interannual (R 2  = 0.80) timescales. At hourly timescales, we found that 75% of observed GEP variability could be attributed to environmental variability. When aggregating GEP to the longer timescales (daily, monthly, and yearly), however, environmental variation explained progressively less GEP variability: At monthly timescales, it explained only 3%, much less than biotic variation in canopy photosynthetic light-use efficiency, which accounted for 63%. These results challenge modeling approaches that assume GEP is primarily controlled by the environment at both short and long timescales. Our approach distinguishing biotic from environmental variability can help to resolve debates about environmental limitations to tropical forest photosynthesis. For example, we found that biotically regulated canopy photosynthetic light-use efficiency (associated with leaf phenology) increased with sunlight during dry seasons (consistent with light but not water limitation of canopy development) but that realized GEP was nonetheless lower relative to its potential efficiency during dry than wet seasons (consistent with water limitation of photosynthesis in given assemblages of leaves). This work highlights the importance of accounting for differential regulation of GEP at different timescales and of identifying the underlying feedbacks and adaptive mechanisms., (© 2016 John Wiley & Sons Ltd.)

Q fever is a worldwide zoonotic disease caused by the pathogen Coxiella (C.) burnetii. A wide range of animal species is susceptible to this intracellular bacterium with great importance in ruminants. Human infections occur mainly by airborne transmission. C burnetii was detected in animal products such as raw milk, raw-milk cheese and butter prepared from raw milk as well as in the meat of infected animals. In cattle milk, the pathogen was detected up to 13 months after calving. The risk of human foodborne C. Burnetii infection is still considered to be low, but cannot be completely ruled out and remains under discussion. The aim of this study was to compare different laboratory diagnostic methods for C. burnetii in milk sample. The bulk tank and individual milk samples were sent and studied at the National Reference Laboratory for Q-fever in the context of confirmatory laboratory testing after clinical suspicion or retesting of previously antibody detection was in the analysis of 888 individual milk samples a match of 93.3% (Cohen-kappa). A total of 173 bulk milk samples and 2,807 individual milk samples from bovine herds for the presence of C. burnetii DNA and antibodies were tested against the pathogen. The pathogen was detected in 62.5% of the bulk milk samples and up to 60% in individual milk samples. The highest proportion of positive bulk milks was determined as 68.3% in 2012. In individual milk samples, the highest proportion of seropositive samples was 62.2%.

Fosalvudine tidoxil is a prodrug derived from the nucleoside reverse transcriptase inhibitor 3-deoxy-3-fluorothymidine (FLT; alovudine). FLT effectively inhibits resistant human immunodeficiency virus type 1, but its clinical development was stopped due to bone marrow and liver toxicity. In this study, we examined the long-term in vivo effects of fosalvudine tidoxil on the mitochondrial DNA (mtDNA) contents in rats. Sprague-Dawley rats received fosalvudine tidoxil (15, 40, or 100 mg/kg of body weight/day) by oral gavage during a period of 8 weeks. Didanosine (100 mg/kg/day) was used as a positive control for mitochondrial toxicity. mtDNA levels in liver, gastrocnemius muscle, sciatic nerve, and inguinal fat pad tissues were quantified by real-time PCR. In hepatic mitochondria, fosalvudine tidoxil induced significant mtDNA depletion. At doses of 15, 40, and 100 mg/kg, the mean hepatic mtDNA values were 62, 64, and 47% of control values, respectively. Rats exposed to 100 mg/kg of fosalvudine tidoxil, unlike all other groups, had slightly elevated levels of glutamate pyruvate transaminase in sera. Didanosine induced a loss of mtDNA (to 48% of the control level) similar to that induced by fosalvudine tidoxil. mtDNA levels in skeletal, neural, and adipose tissues in the negative control and treatment groups were similar. Our results suggest that fosalvudine tidoxil induces mitochondrial hepatotoxicity and that this effect warrants scrutiny in clinical trials.

An intensity-stabilized diode laser absorption spectrometer was developed and used to perform a highly accurate study of the line shape of CO(2) absorption lines, in the spectral region around 5000 cm(-1), belonging to the nu(1) + 2nu(2)(0) + nu(3) combination band, at a temperature of 296.00 K. Standard and complex semiclassical models, including Dicke narrowing and speed-dependent broadening effects, were applied, tested, and compared in the pressure range between 0.7 and 4 kPa, in order to single out the model best reproducing the absorption profile and, hence, the physical situation of self-colliding CO(2) molecules. Line intensity factors and self-broadening coefficients were determined. The 1-sigma overall accuracy of our determinations is at a level of 0.1%, which is, to our knowledge, the highest ever reached.

An intensity-stabilized laser absorption spectrometer, which incorporates a mirror-extended cavity diode laser, a temperature-stabilized gas cell, and a Michelson interferometer, was developed and applied to a highly accurate investigation of line intensity factors within the nu(1)+2nu(2) (0)+nu(3) combination band of carbon dioxide, around 2 microm wavelength, at a temperature of 296.0 K. This relatively complex apparatus enables one to observe the absorption line shape with high precision and accuracy in such a way that it is possible to retrieve the integrated absorbance with a relative uncertainty better than 0.1%. The absorption spectra were interpolated with the uncorrelated strong-collision model of Rautian and Sobel'man in order to take into account Dicke narrowing effects, thus obtaining an agreement at a level of a few parts per 10(-5). We report line strength values for the R(2)-R(18) transitions with an unprecedented level of accuracy, in the range between 0.1% and 0.15%. Finally, we discuss the possibility of providing a first experimental test of the theoretical model for molecular line strengths based on the Herman-Wallis expansion.

The ATP-binding cassette transporter G1 (ABCG1) catalyzes export of cellular cholesterol from macrophages and hepatocytes. Here we identify an additional function of ABCG1 in the regulation of adiposity in screens of the Drosophila melanogaster and the New Zealand obese (NZO) mouse genomes. Insertion of modified transposable elements of the P-family upstream of CG17646, the Drosophila ortholog of Abcg1, generated lines of flies with increased triglyceride stores. In NZO mice, an Abcg1 variant was identified in a suggestive adiposity quantitative trait locus and was associated with higher expression of the gene in white adipose tissue. Targeted disruption of Abcg1 in mice resulted in reduced body weight gain (8.42+/-0.6 g in Abcg1-/- vs. 13.07+/-1.1 g in Abcg1+/+ mice) and adipose tissue mass gain (3.78+/-1.3 g in Abcg1-/- vs. 9.39+/-1.6 g in Abcg1+/+ mice) detected over a period of 12 wk. The reduction of adipose tissue mass in Abcg1-/- mice was associated with markedly decreased size of the adipocytes. In contrast to their wild-type littermates, male Abcg1-/- mice exhibited no high-fat diet-induced impairment of glucose tolerance and fatty liver. Furthermore, Abcg1-/- mice possess decreased food intake and elevated total energy expenditure (Abcg1-/- mice, 748.1+/-5.4 kJ/kg metabolic body mass; Abcg1+/+ mice, 684.3+/-5.0 kJ/kg metabolic body mass; P=0.011), body temperature (Abcg1-/- mice, 37.82+/-0.29 C; Abcg1+/+ mice, 36.83+/-0.24 C; P<0.05), and locomotor activity (Abcg1-/- mice, 3655+/-189 counts/12 h during dark phase; Abcg1+/+ mice, 2445+/-235 counts/12 h during dark phase; P<0.01). Our data indicate a previously unrecognized role of ABCG1 in the regulation of energy balance and triglyceride storage.

Skeletal muscle uncoupling by ectopic expression of mitochondrial uncoupling protein 1 (UCP1) has been shown to result in a lean phenotype in mice characterized by increased energy expenditure (EE), resistance to diet-induced obesity, and improved glucose tolerance. Here, we investigated in detail the effect of ectopic UCP1 expression in skeletal muscle on thermoregulation and energy homeostasis in HSA-mUCP1 transgenic mice. Thermoneutrality was determined to be approximately 30 degrees C for both wild-type (WT) and transgenic mice. EE, body temperature (Tb), activity, and respiratory quotient (RQ) were then measured over 24 h at ambient temperatures (Ta) of 30, 22, and 5 degrees C. HSA-mUCP1 transgenic mice showed increased activity-related EE and heat loss but similar basal metabolic rate compared with WT. Tb at resting periods was progressively decreased with declining Ta in HSA-mUCP1 transgenic mice but not in WT. Compared with WT littermates, the transgenic HSA-mUCP1 mice displayed increased RQ levels during night time, indicative of increased overall glucose oxidation, and failed to decrease their RQ levels with declining Ta. Thus increased EE caused by skeletal muscle uncoupling is clearly due to a decreased muscle energy efficiency during activity combined with increased glucose oxidation and a compromised thermoregulation associated with increased overall heat loss. At Tas below thermoneutrality, this puts increasing energy demands on the animals, whereas at thermoneutrality most differences in energy metabolism are not apparent any more.

We have built a high-resolution and high-signal-to-noise ratio spectrometer for line shape studies of greenhouse gases in the mid infrared. The infrared radiation is generated in a AgGaS2 nonlinear crystal by the well-known difference-frequency method. The choice of crystal is explained, and a brief literature review is presented. With two tunable dye lasers and a type I, 90 degrees phase-matching geometry, the infrared is continuously tunable from 7 to 9 microm when Rhodamine 6G and Sulforhodamine 640 dyes are used. The total infrared power exceeds 30 nW and is limited by both the damage threshold and thermal loading of the crystal. Phase-sensitive detection allows us to reach signal-to-noise ratios in excess of 3500:1 while maintaining an instrumental linewidth of 1.5 MHz. However, we show that the spectrometer may be used to measure the positions of spectral lines within +/-400 kHz.

The temperature and pressure cycles inside a pressure modulator cell (PMC) of the type used for gas-correlation radiometry aboard the Measurements of Pollution in the Troposphere (MOPITT) satellite instrument have been determined from dynamic measurements of the spectral line shapes of the R(0) and R(18) transitions in the fundamental vibrational-rotational band of carbon monoxide. The line strengths and linewidths were used to calculate the temperature and pressure, respectively, with a temporal resolution of approximately 200 micros, or 1/100 of a PMC cycle. The results are compared with a thermodynamic box model.

The past few years have seen an increase in interest about the molecular and genetic events regulating pancreas development. Transcription factors such as Pdx1, p48 and Nkx2.2 have been shown to be essential for the proper differentiation of exocrine and endocrine tissue; however, pancreas development also involves intricate interactions between the pancreatic epithelium and its surrounding mesenchyme. Signalling factors emanating from the notochord have been shown to repress Sonic hedgehog expression in the endoderm whereas signals originating from the pancreatic mesenchyme determine the proportion of exocrine to endocrine tissue. Understanding the molecular and genetic events underlying pancreas development also opens the door for devising new therapeutic strategies against pancreatic diseases such as diabetes and cancer.

Fork head-5 (Fkh5; also known as Mf3 and TWH) is a transcription factor of the winged helix family. As part of an extended project to understand the function of this protein in the developing mouse brain, in the present work we have used Fkh5/Mf3 expression as a marker to study the development of the midbrain and hindbrain. In the midbrain, Fkh5/Mf3 is expressed in the superior colliculus, in the ventricular layer of the inferior colliculus and in the isthmus. In the superior colliculus, Fkh5/Mf3 is expressed by cells of layers 4a and 4c since early in development. In the hindbrain, Fkh5/Mf3 is a longitudinal marker (as opposed to a transverse or rhombomeric one), since it labels nuclei belonging to the somatic afferent zone (ventral cochlear nucleus, cuneate and external cuneate nuclei, principal and spinal nuclei of the trigeminal). In addition, Fkh5/Mf3 is expressed by the developing endopiriform nucleus and by the olivary pretectal nucleus. The results suggest that Fkh5/Mf3 has an early role in the lamination of the tectum and in the longitudinal differentiation of the hindbrain., (Copyright 1998 Elsevier Science B.V.)

We isolated a murine homeobox containing gene, Uncx4.1. The homeodomain sequence exhibits 88% identity to the unc-4 protein at the amino acid level. In situ hybridization analysis revealed that Uncx4.1 is expressed in the paraxial mesoderm, in the developing kidney, and central nervous system. The most intriguing expression domain is the somite, where it is confined to the caudal part of the newly formed somite and subsequently restricted to the caudal domain of the developing sclerotome. In the central nervous system, Uncx4.1 is detected in the developing spinal cord, hindbrain, mesencephalon, and telencephalon. The temporal and spatial expression pattern suggests that Uncx4.1 may play an important role in kidney development and in the differentiation of the sclerotome and the nervous system.

Pax genes encode transcription factors sharing a highly conserved sequence, the paired box. Their temporally and spatially restricted expression patterns during development indicate that Pax genes are involved in important steps of nervous system formation. Mutations in Pax genes have been correlated with three mouse mutants (undulated, splotch, small eye) and two human diseases (Waardenburg syndrome, aniridia). Recent data demonstrated that deregulation of Pax genes contributes to tumor formation.