CRF receptors in the rodent and human cardiovascular systems: Species differences

CRF has powerful receptor-mediated cardiovascular actions. To evaluate the precise distribution of CRF receptors, in vitro CRF receptor autoradiography with (125)I-[Tyr(0), Glu(1), Nle(17)]-sauvagine or [(125)I]-antisauvagine-30 was performed in the rodent and human cardiovascular system. An extremely high density of CRF(2) receptors was detected with both tracers in vessels of rodent lung, intestine, pancreas, mesenterium, kidney, urinary bladder, testis, heart, brain, and in heart muscle. In humans, CRF(2) receptors were detected with (125)I- antisauvagine-30 at low levels in vessels of kidneys, intestine, urinary bladder, testis, heart and in heart muscle, while only heart vessels were detected with (125)I-[Tyr(0), Glu(1), Nle(17)]-sauvagine. This is the first extensive morphological study reporting the extremely wide distribution of CRF(2) receptors in the rodent cardiovascular system and a more limited expression in man, suggesting a species-selective CRF receptor expression.

Self-assembly of sensory neurons into ganglia-like microtissues

Unraveling intra- and inter-cellular signaling networks managing cell-fate control, coordinating complex differentiation regulatory circuits and shaping tissues and organs in living systems remain major challenges in the post-genomic era. Resting on the laurels of past-century monolayer culture technologies, the cell culture community has only recently begun to appreciate the potential of three-dimensional mammalian cell culture systems to reveal the full scope of mechanisms orchestrating the tissue-like cell quorum in space and time. Capitalizing on gravity-enforced self-assembly of monodispersed primary embryonic mouse cells in hanging drops, we designed and characterized a three-dimensional cell culture model for ganglion-like structures. Within 24h, a mixture of mouse embryonic fibroblasts (MEF) and cells, derived from the dorsal root ganglion (DRG) (sensory neurons and Schwann cells) grown in hanging drops, assembled to coherent spherical microtissues characterized by a MEF feeder core and a peripheral layer of DRG-derived cells. In a time-dependent manner, sensory neurons formed a polar ganglion-like cap structure, which coordinated guided axonal outgrowth and innervation of the distal pole of the MEF feeder spheroid. Schwann cells, present in embryonic DRG isolates, tended to align along axonal structures and myelinate them in an in vivo-like manner. Whenever cultivation exceeded 10 days, DRG:MEF-based microtissues disintegrated due to an as yet unknown mechanism. Using a transgenic MEF feeder spheroid, engineered for gaseous acetaldehyde-inducible interferon-beta (ifn-beta) production by cotransduction of retro-/ lenti-viral particles, a short 6-h ifn-beta induction was sufficient to rescue the integrity of DRG:MEF spheroids and enable long-term cultivation of these microtissues. In hanging drops, such microtissues fused to higher-order macrotissue-like structures, which may pave the way for sophisticated bottom-up tissue engineering strategies. DRG:MEF-based artificial micro- and macrotissue design demonstrated accurate key morphological aspects of ganglions and exemplified the potential of self-assembled scaffold-free multicellular micro-/macrotissues to provide new insight into organogenesis.

Bayesian Hierarchical Distributed Lag Models for Summer Ozone Exposure and Cardio-Respiratory Mortality

In this paper, we develop Bayesian hierarchical distributed lag models for estimating associations between daily variations in summer ozone levels and daily variations in cardiovascular and respiratory (CVDRESP) mortality counts for 19 U.S. large cities included in the National Morbidity Mortality Air Pollution Study (NMMAPS) for the period 1987 - 1994. At the first stage, we define a semi-parametric distributed lag Poisson regression model to estimate city-specific relative rates of CVDRESP associated with short-term exposure to summer ozone. At the second stage, we specify a class of distributions for the true city-specific relative rates to estimate an overall effect by taking into account the variability within and across cities. We perform the calculations with respect to several random effects distributions (normal, t-student, and mixture of normal), thus relaxing the common assumption of a two-stage normal-normal hierarchical model. We assess the sensitivity of the results to: 1) lag structure for ozone exposure; 2) degree of adjustment for long-term trends; 3) inclusion of other pollutants in the model;4) heat waves; 5) random effects distributions; and 6) prior hyperparameters. On average across cities, we found that a 10ppb increase in summer ozone level for every day in the previous week is associated with 1.25 percent increase in CVDRESP mortality (95% posterior regions: 0.47, 2.03). The relative rate estimates are also positive and statistically significant at lags 0, 1, and 2. We found that associations between summer ozone and CVDRESP mortality are sensitive to the confounding adjustment for PM_10, but are robust to: 1) the adjustment for long-term trends, other gaseous pollutants (NO_2, SO_2, and CO); 2) the distributional assumptions at the second stage of the hierarchical model; and 3) the prior distributions on all unknown parameters. Bayesian hierarchical distributed lag models and their application to the NMMAPS data allow us estimation of an acute health effect associated with exposure to ambient air pollution in the last few days on average across several locations. The application of these methods and the systematic assessment of the sensitivity of findings to model assumptions provide important epidemiological evidence for future air quality regulations.

A gas ion source for radiocarbon measurements at 200 kV

The novel tabletop miniaturized radiocarbon dating system (MICADAS) at ETH Zurich features a hybrid Cs sputter negative ion source for the measurement of solid graphite and gaseous CO2 samples. The source produces stable currents of up to 6 mu A C- out of gaseous samples with an efficiency of 3-6%. A gas feeding system has been set up that enables constant dosing of CO2 into the Cs sputter ion source and ensures stable measuring conditions. The system is based on a syringe in which CO2 gas is mixed with He and then pressed continuously into the ion source at a constant flow rate. Minimized volumes allow feeding samples of 3-30 mu g carbon quantitatively into the ion source. In order to test the performance of the system, several standards and blanks have successfully been measured. The ratios of C-14/C-12 could be repeated within statistical errors to better than 1.0% and the C-13/C-12 ratios to better than 0.2%. The blank was < 1 pMC.

Functional respiratory morphology in the newborn quokka wallaby (Setonix brachyurus)

A morphological and morphometric study of the lung of the newborn quokka wallaby (Setonix brachyurus) was undertaken to assess its morphofunctional status at birth. Additionally, skin structure and morphometry were investigated to assess the possibility of cutaneous gas exchange. The lung was at canalicular stage and comprised a few conducting airways and a parenchyma of thick-walled tubules lined by stretches of cuboidal pneumocytes alternating with squamous epithelium, with occasional portions of thin blood-gas barrier. The tubules were separated by abundant intertubular mesenchyme, aggregations of developing capillaries and mesenchymal cells. Conversion of the cuboidal pneumocytes to type I cells occurred through cell broadening and lamellar body extrusion. Superfluous cuboidal cells were lost through apoptosis and subsequent clearance by alveolar macrophages. The establishment of the thin blood-gas barrier was established through apposition of the incipient capillaries to the formative thin squamous epithelium. The absolute volume of the lung was 0.02 +/- 0.001 cm(3) with an air space surface area of 4.85 +/- 0.43 cm(2). Differentiated type I pneumocytes covered 78% of the tubular surface, the rest 22% going to long stretches of type II cells, their precursors or low cuboidal transitory cells with sparse lamellar bodies. The body weight-related diffusion capacity was 2.52 +/- 0.56 mL O(2) min(-1) kg(-1). The epidermis was poorly developed, and measured 29.97 +/- 4.88 microm in thickness, 13% of which was taken by a thin layer of stratum corneum, measuring 4.87 +/- 0.98 microm thick. Superficial capillaries were closely associated with the epidermis, showing the possibility that the skin also participated in some gaseous exchange. Qualitatively, the neonate quokka lung had the basic constituents for gas exchange but was quantitatively inadequate, implying the significance of percutaneous gas exchange.

Nitric oxide synthase protein levels, not the mRNA, are downregulated in olfactory bulb interneurons of reeler mice

Homozygous mutations in the Reelin gene result in severe disruption of brain development. The histogenesis of layered regions, like the neocortex, hippocampus and the cerebellum, is most notably affected in mouse reeler mutants and similar traits are also present in mice lacking molecular components of the Reelin signalling pathway. Moreover, there is evidence for an additional role of Reelin in sustaining synaptic plasticity in adult networks. Nitric oxide is an important gaseous messenger that can modulate neuronal plasticity both in developing and mature synaptic networks and has been shown to facilitate synaptic changes in the hippocampus, cerebellum and olfactory bulb. We studied the distribution and content of neuronal nitric oxide synthase in the olfactory bulbs of reeler and wildtype mice. Immunocytochemistry reveals that Reelin and neuronal nitric oxide synthase containing interneurons are two distinct, non overlapping cell populations of the olfactory bulb. We show by in situ hybridization that both nitrergic and Reelin expressing cells represent only a subset of olfactory bulb GABAergic neurons. Immunoblots show that neuronal nitric oxide synthase protein content is decreased by two thirds in reeler mice causing a detectable loss of immunolabelled cells throughout the olfactory bulb of this strain. However, neuronal nitric oxide synthase mRNA levels, essayed by quantitative real-time RT-PCR, are unaffected in the reeler olfactory bulb. Thus, disruption of the Reelin signalling pathway may modify the turnover of neuronal nitric oxide synthase in the olfactory bulb and possibly affects nitric oxide functions in reeler mice.

Treating sensitive cervical areas with ozone. A prospective controlled clinical trial

PURPOSE: To determine whether the treatment of hypersensitive teeth with gaseous ozone (Healozone, KaVo 1600 ppm) for 60 seconds reduces pain immediately after treatment and in the longer term. METHODS: In three private practices in Switzerland, 31 subjects suffering from hypersensitive teeth were treated with gaseous ozone over a period of 54 weeks (one test and one control tooth in each subject). A cross-over design was chosen. The pain level was measured with a Visual Analogue Scale before and after the treatment. RESULTS: The subjects' pain level was reduced by 55% +/- 5.5% immediately after the ozone treatment. Over time, the pain level decreased significantly in all groups: The pain level in the test teeth was significantly reduced in Weeks 0-22 (treatment group, P < 0.001) compared to the pain level before treatment. The pain level in the control group was also reduced significantly over time in Weeks 0-22 (no-treatment, P = 0.025) and in Weeks 22-54 (treatment group, P = 0.0065). Comparing test and control teeth over time, there was no statistically significant difference in pain reduction (P = 0.58).

Peptide-based probes for cancer imaging

Receptors for regulatory peptides are overexpressed in a variety of human cancers. They represent the molecular basis for in vivo imaging with radiolabeled peptide probes. Somatostatin-derived tracers, designed to image the sst2-overexpressing neuroendocrine tumors, have enjoyed almost 2 decades of successful development and extensive clinical applications. More recent developments include second- and third-generation somatostatin analogs, with a broader receptor subtype profile or with antagonistic properties. Emerging tracers for other peptide receptors, including cholecystokinin/gastrin and GLP-1 analogs for neuroendocrine tumors, bombesin and neuropeptide-Y analogs for prostate or breast cancers, or Arg-Gly-Asp peptides for neoangiogenesis labeling, are also in current development. Application fields include both SPECT/CT and PET/CT.

Experimental and modeling study of the filtration and oxidation characteristics of a diesel oxidation catalyst and a catalyzed particulate filter

A diesel oxidation catalyst (DOC) with a catalyzed diesel particulate filter (CPF) is an effective exhaust aftertreatment device that reduces particulate emissions from diesel engines, and properly designed DOC-CPF systems provide passive regeneration of the filter by the oxidation of PM via thermal and NO2/temperature-assisted means under various vehicle duty cycles. However, controlling the backpressure on engines caused by the addition of the CPF to the exhaust system requires a good understanding of the filtration and oxidation processes taking place inside the filter as the deposition and oxidation of solid particulate matter (PM) change as functions of loading time. In order to understand the solid PM loading characteristics in the CPF, an experimental and modeling study was conducted using emissions data measured from the exhaust of a John Deere 6.8 liter, turbocharged and after-cooled engine with a low-pressure loop EGR system and a DOC-CPF system (or a CCRT® - Catalyzed Continuously Regenerating Trap®, as named by Johnson Matthey) in the exhaust system. A series of experiments were conducted to evaluate the performance of the DOC-only, CPF-only and DOC-CPF configurations at two engine speeds (2200 and 1650 rpm) and various loads on the engine ranging from 5 to 100% of maximum torque at both speeds. Pressure drop across the DOC and CPF, mass deposited in the CPF at the end of loading, upstream and downstream gaseous and particulate emissions, and particle size distributions were measured at different times during the experiments to characterize the pressure drop and filtration efficiency of the DOCCPF system as functions of loading time. Pressure drop characteristics measured experimentally across the DOC-CPF system showed a distinct deep-bed filtration region characterized by a non-linear pressure drop rise, followed by a transition region, and then by a cake-filtration region with steadily increasing pressure drop with loading time at engine load cases with CPF inlet temperatures less than 325 °C. At the engine load cases with CPF inlet temperatures greater than 360 °C, the deep-bed filtration region had a steep rise in pressure drop followed by a decrease in pressure drop (due to wall PM oxidation) in the cake filtration region. Filtration efficiencies observed during PM cake filtration were greater than 90% in all engine load cases. Two computer models, i.e., the MTU 1-D DOC model and the MTU 1-D 2-layer CPF model were developed and/or improved from existing models as part of this research and calibrated using the data obtained from these experiments. The 1-D DOC model employs a three-way catalytic reaction scheme for CO, HC and NO oxidation, and is used to predict CO, HC, NO and NO2 concentrations downstream of the DOC. Calibration results from the 1-D DOC model to experimental data at 2200 and 1650 rpm are presented. The 1-D 2-layer CPF model uses a ‘2-filters in series approach’ for filtration, PM deposition and oxidation in the PM cake and substrate wall via thermal (O2) and NO2/temperature-assisted mechanisms, and production of NO2 as the exhaust gas mixture passes through the CPF catalyst washcoat. Calibration results from the 1-D 2-layer CPF model to experimental data at 2200 rpm are presented. Comparisons of filtration and oxidation behavior of the CPF at sample load-cases in both configurations are also presented. The input parameters and selected results are also compared with a similar research work with an earlier version of the CCRT®, to compare and explain differences in the fundamental behavior of the CCRT® used in these two research studies. An analysis of the results from the calibrated CPF model suggests that pressure drop across the CPF depends mainly on PM loading and oxidation in the substrate wall, and also that the substrate wall initiates PM filtration and helps in forming a PM cake layer on the wall. After formation of the PM cake layer of about 1-2 µm on the wall, the PM cake becomes the primary filter and performs 98-99% of PM filtration. In all load cases, most of PM mass deposited was in the PM cake layer, and PM oxidation in the PM cake layer accounted for 95-99% of total PM mass oxidized during loading. Overall PM oxidation efficiency of the DOC-CPF device increased with increasing CPF inlet temperatures and NO2 flow rates, and was higher in the CCRT® configuration compared to the CPF-only configuration due to higher CPF inlet NO2 concentrations. Filtration efficiencies greater than 90% were observed within 90-100 minutes of loading time (starting with a clean filter) in all load cases, due to the fact that the PM cake on the substrate wall forms a very efficient filter. A good strategy for maintaining high filtration efficiency and low pressure drop of the device while performing active regeneration would be to clean the PM cake filter partially (i.e., by retaining a cake layer of 1-2 µm thickness on the substrate wall) and to completely oxidize the PM deposited in the substrate wall. The data presented support this strategy.

Comprehensive review and application of particle image velocimetry

For a fluid dynamics experimental flow measurement technique, particle image velocimetry (PIV) provides significant advantages over other measurement techniques in its field. In contrast to temperature and pressure based probe measurements or other laser diagnostic techniques including laser Doppler velocimetry (LDV) and phase Doppler particle analysis (PDPA), PIV is unique due to its whole field measurement capability, non-intrusive nature, and ability to collect a vast amount of experimental data in a short time frame providing both quantitative and qualitative insight. These properties make PIV a desirable measurement technique for studies encompassing a broad range of fluid dynamics applications. However, as an optical measurement technique, PIV also requires a substantial technical understanding and application experience to acquire consistent, reliable results. Both a technical understanding of particle image velocimetry and practical application experience are gained by applying a planar PIV system at Michigan Technological University’s Combustion Science Exploration Laboratory (CSEL) and Alternative Fuels Combustion Laboratory (AFCL). Here a PIV system was applied to non-reacting and reacting gaseous environments to make two component planar PIV as well as three component stereographic PIV flow field velocity measurements in conjunction with chemiluminescence imaging in the case of reacting flows. This thesis outlines near surface flow field characteristics in a tumble strip lined channel, three component velocity profiles of non-reacting and reacting swirled flow in a swirl stabilized lean condition premixed/prevaporized-fuel model gas turbine combustor operating on methane at 5-7 kW, and two component planar PIV measurements characterizing the AFCL’s 1.1 liter closed combustion chamber under dual fan driven turbulent mixing flow.

Nano-engineering of composite material via reactive mechanical alloying/milling (RMA/M)

Attempts to strengthen a chromium-modified titanium trialuminide by a combination of grain size refinement and dispersoid strengthening led to a new means to synthesize such materials. This Reactive Mechanical Alloying/Milling process uses in situ reactions between the metallic powders and elements from a process control agent and/or a gaseous environment to assemble a dispersed small hard particle phase within the matrix by a bottom-up approach. In the current research milled powders of the trialuminide alloy along with titanium carbide were produced. The amount of the carbide can be varied widely with simple processing changes and in this case the milling process created trialuminide grain sizes and carbide particles that are the smallest known from such a process. Characterization of these materials required the development of x-ray diffraction means to determine particle sizes by deconvoluting and synthesizing components of the complex multiphase diffraction patterns and to carry out whole pattern analysis to analyze the diffuse scattering that developed from larger than usual highly defective grain boundary regions. These identified regions provide an important mass transport capability in the processing and not only facilitate the alloy development, but add to the understanding of the mechanical alloying process. Consolidation of the milled powder that consisted of small crystallites of the alloy and dispersed carbide particles two nanometers in size formed a unique, somewhat coarsened, microstructure producing an ultra-high strength solid material composed of the chromium-modified titanium trialuminide alloy matrix with small platelets of the complex carbides Ti2AlC and Ti3AlC2. This synthesis process provides the unique ability to nano-engineer a wide variety of composite materials, or special alloys, and has shown the ability to be extended to a wide variety of metallic materials.

PROPERTIES AND STRUCTURES OF Li-N BASED HYDROGEN STORAGE MATERIALS

Traditional transportation fuel, petroleum, is limited and nonrenewable, and it also causes pollutions. Hydrogen is considered one of the best alternative fuels for transportation. The key issue for using hydrogen as fuel for transportation is hydrogen storage. Lithium nitride (Li3N) is an important material which can be used for hydrogen storage. The decompositions of lithium amide (LiNH2) and lithium imide (Li2NH) are important steps for hydrogen storage in Li3N. The effect of anions (e.g. Cl-) on the decomposition of LiNH2 has never been studied. Li3N can react with LiBr to form lithium nitride bromide Li13N4Br which has been proposed as solid electrolyte for batteries. The decompositions of LiNH2 and Li2NH with and without promoter were investigated by using temperature programmed decomposition (TPD) and X-ray diffraction (XRD) techniques. It was found that the decomposition of LiNH2 produced Li2NH and NH3 via two steps: LiNH2 into a stable intermediate species (Li1.5NH1.5) and then into Li2NH. The decomposition of Li2NH produced Li, N2 and H2 via two steps: Li2NH into an intermediate species --- Li4NH and then into Li. The kinetic analysis of Li2NH decomposition showed that the activation energies are 533.6 kJ/mol for the first step and 754.2 kJ/mol for the second step. Furthermore, XRD demonstrated that the Li4NH, which was generated in the decomposition of Li2NH, formed a solid solution with Li2NH. In the solid solution, Li4NH possesses a similar cubic structure as Li2NH. The lattice parameter of the cubic Li4NH is 0.5033nm. The decompositions of LiNH2 and Li2NH can be promoted by chloride ion (Cl-). The introduction of Cl- into LiNH2 resulted in the generation of a new NH3 peak at low temperature of 250 °C besides the original NH3 peak at 330 °C in TPD profiles. Furthermore, Cl- can decrease the decomposition temperature of Li2NH by about 110 °C. The degradation of Li3N was systematically investigated with techniques of XRD, Fourier transform infrared (FT-IR) spectroscopy, and UV-visible spectroscopy. It was found that O2 could not affect Li3N at room temperature. However, H2O in air can cause the degradation of Li3N due to the reaction between H2O and Li3N to LiOH. The produced LiOH can further react with CO2 in air to Li2CO3 at room temperature. Furthermore, it was revealed that Alfa-Li3N is more stable in air than Beta-Li3N. The chemical stability of Li13N4Br in air has been investigated by XRD, TPD-MS, and UV-vis absorption as a function of time. The aging process finally leads to the degradation of the Li13N4Br into Li2CO3, lithium bromite (LiBrO2) and the release of gaseous NH3. The reaction order n = 2.43 is the best fitting for the Li13N4Br degradation in air reaction. Li13N4Br energy gap was calculated to be 2.61 eV.

IMPACT OF 2000-2050 CLIMATE CHANGE ON GLOBAL ATMOSPHERIC TRANSPORT AND DEPOSITION OF MERCURY

Since it is very toxic and accumulates in organisms, particularly in fish, mercury is a very important pollutant and one of the most studies. And this concern over the toxicity and human health risks of mercury has prompted efforts to regulate anthropogenic emissions. As mercury pollution problem is getting increasingly serious, we are curious about how serious this problem will be in the future. What is more, how the climate change in the future will affect the mercury concentration in the atmosphere. So we investigate the impact of climate change on mercury concentration in the atmosphere. We focus on the comparison between the mercury data for year 2000 and for year 2050. The GEOS-Chem model shows that the mercury concentrations for all tracers (1 to 3), elemental mercury (Hg(0)), divalent mercury (Hg(II)) and primary particulate mercury (Hg(P)) have differences between 2000 and 2050 in most regions over the world. From the model results, we can see the climate change from 2000 to 2050 would decrease Hg(0) surface concentration in most of the world. The driving factors of Hg(0) surface concentration changes are natural emissions(ocean and vegetation) and the transformation reactions between Hg(0) and Hg(II). The climate change from 2000 to 2050 would increase Hg(II) surface concentration in most of mid-latitude continental parts of the world while decreasing Hg(II) surface concentration in most of high-latitude part of the world. The driving factors of Hg(II) surface concentration changes is deposition amount change (majorly wet deposition) from 2000 to 2050 and the transformation reactions between Hg(0) and Hg(II). Climate change would increase Hg(P) concentration in most of mid-latitude area of the world and meanwhile decrease Hg(P) concentration in most of high-latitude regions of the world. For the Hg(P) concentration changes, the major driving factor is the deposition amount change (mainly wet deposition) from 2000 to 2050.

Identification of glacial meltwater runoff in a karstic environment and its implication for present and future water availability

Glaciers all over the world are expected to continue to retreat due to the global warming throughout the 21st century. Consequently, future seasonal water availability might become scarce once glacier areas have declined below a certain threshold affecting future water management strategies. Particular attention should be paid to glaciers located in a karstic environment, as parts of the meltwater can be drained by underlying karst systems, making it difficult to assess water availability. In this study tracer experiments, karst modeling and glacier melt modeling are combined in order to identify flow paths in a high alpine, glacierized, karstic environment (Glacier de la Plaine Morte, Switzerland) and to investigate current and predict future downstream water availability. Flow paths through the karst underground were determined with natural and fluorescent tracers. Subsequently, geologic information and the findings from tracer experiments were assembled in a karst model. Finally, glacier melt projections driven with a climate scenario were performed to discuss future water availability in the area surrounding the glacier. The results suggest that during late summer glacier meltwater is rapidly drained through well-developed channels at the glacier bottom to the north of the glacier, while during low flow season meltwater enters into the karst and is drained to the south. Climate change projections with the glacier melt model reveal that by the end of the century glacier melt will be significantly reduced in the summer, jeopardizing water availability in glacier-fed karst springs.

The SLC3 and SLC7 families of amino acid transporters

Amino acids are necessary for all living cells and organisms. Specialized transporters mediate the transfer of amino acids across plasma membranes. Malfunction of these proteins can affect whole-body homoeostasis giving raise to diverse human diseases. Here, we review the main features of the SLC3 and SLC7 families of amino acid transporters. The SLC7 family is divided into two subfamilies, the cationic amino acid transporters (CATs), and the L-type amino acid transporters (LATs). The latter are the light or catalytic subunits of the heteromeric amino acid transporters (HATs), which are associated by a disulfide bridge with the heavy subunits 4F2hc or rBAT. These two subunits are glycoproteins and form the SLC3 family. Most CAT subfamily members were functionally characterized and shown to function as facilitated diffusers mediating the entry and efflux of cationic amino acids. In certain cells, CATs play an important role in the delivery of L-arginine for the synthesis of nitric oxide. HATs are mostly exchangers with a broad spectrum of substrates and are crucial in renal and intestinal re-absorption and cell redox balance. Furthermore, the role of the HAT 4F2hc/LAT1 in tumor growth and the application of LAT1 inhibitors and PET tracers for reduction of tumor progression and imaging of tumors are discussed. Finally, we describe the link between specific mutations in HATs and the primary inherited aminoacidurias, cystinuria and lysinuric protein intolerance.