Em bovinos de corte, maiores diâmetros do folículo pré-ovulatório (FPO) e as subsequentes altas concentrações de progesterona [P4] aumentam o crescimento do concepto e a taxa de prenhez. Formulou-se a hipótese que a modulação do tamanho do FPO e [P4] no diestro subsequente à ovulação do FPO estimulam a expressão endometrial de transcritos e proteínas da famílias das Solute Carrier Proteins (SLC) que estão relacionadas ao transporte de glicose. Vacas Nelore (n=60), solteiras e ciclando receberam duas injeções de PGF2&alpha; (PGF; 0,5mg; i.m.) com intervalo de 14 dias. Dez dias após (dia -10; D-10), receberam um dispositivo intravaginal liberador de P4 e benzoato de estradiol (2mg; i.m.). Para modular o crescimento do FPO e alterar a produção de P4 pós-ovulação, no D-10 os animais receberam PGF (grupo alta P4; AP) ou não (grupo baixa P4; BP). Dispositivos foram removidos e PGF injetada 60 a 42 horas antes da indução da ovulação para o grupo AP e 48 a 30 horas antes da indução para o grupo BP e ovulações foram induzidas com GnRH (buserelina; 10&micro;g; i.m.) no D0. Crescimento e ovulação do FPO e formação do CL foram avaliados por ultrassom e [P4] medidas por radioimunoensaio. No D7 os animais que ovularam foram abatidos (AP, N=18 e BP, N=18), o endométrio foi dissecado e submetido à extração de RNA total para análises de qPCR, extração de proteínas totais para análises de western blotting e incluído em parafina para análises de imunohistoquímica. Diferença entre as médias dos grupos foi determinada pelo teste t de student. O diâmetro máximo do FPO (média ± erro padrão da média; 12,8±0,4 vs. 11,1±0,4mm) foi maior no grupo AP (P<0,01). A [P4] no D7 foi maior no grupo AP (4,5±1,0 ng/mL vs. 3,3±1,1 ng/mL; P<0,05). As concentrações relativas dos transcritos que codificam SLCs foram determinadas por qPCR, usando a ciclofilina como controle endógeno. Não houve diferença na expressão de SLC2A1 (0,91±0,04 vs. 1,02±0,07), SLC2A3 (1,14±0,16 vs. 1,05±0,1), SLC2A4 (1,20±0,14 vs. 1,01±0,05), SLC2A5 (0,95±0,12 vs. 1,04±0,12), SLC5A1 (1,35±0,25 vs. 1,49±0,44), ATP1A2 (1,29±0,17 vs. 1,03±0,1), ATP1B2 (1,20±0,11 vs. 1,06±0,1), SLC37A4 (1,16±0,16 vs. 1,1±0,12), entre os grupos AP e BP respectivamente (P>0.05). Também não foi possível identificar diferença na quantidade proteica de SLC2A1 no endométrio dos animais do grupo AP em relação ao grupo BP. SLC2A1 foi identificada na membrana basal no epitélio luminal (EL), epitélio glandular (EG) e no estroma uterino dos animais. SLC2A4 foi identificada na membrana basal e membrana apical no EL, EG e no estroma uterino dos animais. Em conclusão, a modulação do tamanho do FPO e [P4] no diestro não afetaram a expressão gênica ou proteica dos transportadores de glicose. É possível que ao invés da expressão gênica ou proteica, a atividade transportadora das SLCs, ou ainda, a expressão e função de genes relacionados ao metabolismo de carboidratos, sejam regulados pelo ambiente endócrino peri-ovulatório em vacas. / In beef cattle, changes in the peri-ovulatory endocrine milieu are associated with conceptus growth and fertility. A large size of the pre-ovulatory follicle (POF) and resulting elevated progesterone (P4) concentrations during diestrus affect pregnancy rates positively. Our hypothesis is that modulation of POF size and diestrus P4 concentrations regulate nutrient availability in the uterus. Specifically, optimal glucose concentrations in the histotroph are required for adequate embryo growth during early gestation. The objective was to determine if POF size and resulting P4 concentrations during the first week of diestrus influence gene expression of Solute Carrier Protein (SLC) families that are related to glucose transport. Cyclic, non-lactating Nelore cows received two injections of cloprostenol (PGF; 0.5mg; i.m.) 14 days apart. Ten days later (day -10; D-10), cows received a P4-releasing device along with estradiol benzoate (2mg; i.m.). To modulate the growth of the POF and alter post-ovulatory P4 production, on D-10 animals received PGF (high post-ovulatory P4 group; HP) or not (low post-ovulatory P4 group; LP). The P4-releasing devices were removed and PGF injected 60 to 42 hours before the ovulation induction in the HP group and 48 to 30 hours before the ovulation induction in the LP group. Ovulation was induced with buserelin (GnRH; 10&micro;g; i.m.) on D0. Diameter of POF and ovulation were assessed by ultrasonography starting onD- 2. From D1 to D7, plasma was obtained for measurement of P4 concentration. On D7, cows that ovulated were slaughtered (HP, n=18 and LP, n=18) and endometrium was dissected and subjected total RNA extraction for qPCR analyzes, total protein extraction for western blotting analyzes and included in paraffin for imunohistochemical analyzes. Differences between group means were determined by student\'s t test. Maximum diameter of the POF (mean ± SEM; 12.8±0.4 vs. 11.1±0.4mm) was greater in HP vs. LP (P<0.01). Progesterone concentration on D7 was larger on the HP group (4.5±1.0 ng/mL and 3.3±1.1 ng/mL; P<0.05). Relative concentrations of transcripts coding for facilitative sugar transporters (SLC2A1, SLC2A3, SLC2A4 and SLC2A5), a sodium-dependent glucose co-transporter (SLC5A1) and other transporters related to glucose uptake (ATP1A2, ATP1B2, SLC37A4) were determined by qPCR, using cyclophilin as the endogenous control gene. There were no significant differences in expression of SLC2A1 (mean ± SEM;0.91±0.04 vs. 1.02±0.07), SLC2A3 (1.14±0.16 vs. 1.05±0.1), SLC2A4 (1.20±0.14 vs. 1.01±0.05), SLC2A5 (0.95±0.12 vs. 1.04±0.12), SLC5A1 (1.35±0.25 vs. 1.49±0.44), ATP1A2 (1.29±0.17 vs. 1.03±0.1), ATP1B2 (1.20±0.11 VS. 1.06±0.1) ,SLC37A4 (1.16±0.16 vs. 1.1±0.12), between HP and LP, respectively (P>0.05). There was no difference in the abundance of SLC2A1 protein between groups. The SLC2A1 protein was localized in the luminal epithelium (LE), glandular epithelium (GE) and uterine stroma (US) of animals. The SLC2A4 protein was localized on the basal and apical membrane of the LE, GE and US of animals. In conclusion, modulation of POF size and diestrus P4 concentrations did not affect the expression of glucose transporter genes or proteins. It is possible that activity of SLC proteins rather than gene expression, or alternatively, expression and function of genes related to carbohydrate metabolism, are regulated by the peri-ovulatory endocrine milieu in cows.

Tracer methods are commonly used for estimation of soil water and groundwater recharge flux especially in arid and semiarid regions. These tracer methods are based on the solute profile shape (distribution of concentration with depth) and peak position. For soils of semi-arid to sub-humid climates, vertical water movement may seasonally vary in direction due to climate conditions and vegetative demands. The first objective of this thesis was to show that TDR (time domain reflectometry) can be a useful tool for estimation of soil water fluxes using tracer methods. The second objective was to study the effects of repeated cycles of directionally-varying flow upon solute profile shape and position used by tracer methods under controlled laboratory conditions. Three soil columns with a KCl tracer and Beaver Creek sand were used for this study. Rain and evaporative systems were used to cause the downward and upward soil water movements in the column, respectively. Soil moisture content and solute concentration were measured using TDR.<p> The result for the first objective was that the peak migration and the soil water balance methods gave similar average upward and downward soil water fluxes. This result indicates that the TDR method can be recommended for determination of soil water fluxes with tracer methods in fields or in laboratory studies for sufficient time and depth.<p> In the second objective, three different seasonal flow regimes were studied using the sand columns, and each flow regime simulated climatic seasons that might occur in the field. Several apparent and statistical parameters were used to evaluate the change of the solute profile shape and position under cycling conditions of the three different flow regimes. These parameters showed that the solute profile shape and position clearly changed under the three different repeated regimes of downward and upward seasonal flows. It was concluded that climate (seasonality) can have significant impacts on the estimation of soil water fluxes using tracer methods. The result from this investigation shows that the profile shape and position after a number of cycles (years of fluctuations) can provide a description of the previous climatic effects on the concentration profile. Therefore, the profile shape can be used as an indicator of the flow regime that has affected the solute profile shape. Moreover, if a reference of a solute profile is available (a solute profile before a period of time), it is easier to determine the flow regime affected the profile shape and position by determining the change of the profile shape and position using statistical parameters presented in this thesis.

Tracer methods are commonly used for estimation of soil water and groundwater recharge flux especially in arid and semiarid regions. These tracer methods are based on the solute profile shape (distribution of concentration with depth) and peak position. For soils of semi-arid to sub-humid climates, vertical water movement may seasonally vary in direction due to climate conditions and vegetative demands. The first objective of this thesis was to show that TDR (time domain reflectometry) can be a useful tool for estimation of soil water fluxes using tracer methods. The second objective was to study the effects of repeated cycles of directionally-varying flow upon solute profile shape and position used by tracer methods under controlled laboratory conditions. Three soil columns with a KCl tracer and Beaver Creek sand were used for this study. Rain and evaporative systems were used to cause the downward and upward soil water movements in the column, respectively. Soil moisture content and solute concentration were measured using TDR.<p> The result for the first objective was that the peak migration and the soil water balance methods gave similar average upward and downward soil water fluxes. This result indicates that the TDR method can be recommended for determination of soil water fluxes with tracer methods in fields or in laboratory studies for sufficient time and depth.<p> In the second objective, three different seasonal flow regimes were studied using the sand columns, and each flow regime simulated climatic seasons that might occur in the field. Several apparent and statistical parameters were used to evaluate the change of the solute profile shape and position under cycling conditions of the three different flow regimes. These parameters showed that the solute profile shape and position clearly changed under the three different repeated regimes of downward and upward seasonal flows. It was concluded that climate (seasonality) can have significant impacts on the estimation of soil water fluxes using tracer methods. The result from this investigation shows that the profile shape and position after a number of cycles (years of fluctuations) can provide a description of the previous climatic effects on the concentration profile. Therefore, the profile shape can be used as an indicator of the flow regime that has affected the solute profile shape. Moreover, if a reference of a solute profile is available (a solute profile before a period of time), it is easier to determine the flow regime affected the profile shape and position by determining the change of the profile shape and position using statistical parameters presented in this thesis.

A modification in an existing water uptake and solute transport numerical model was implemented in order to allow the model to simulate solute uptake by the roots. The convection-dispersion equation (CDE) was solved numerically, using a complete implicit scheme, considering a transient state for water and solute fluxes and a soil solute concentration dependent boundary for the uptake at the root surface, based on the Michaelis- Menten (MM) equation. Additionally, a linear approximation was developed for the MM equation such that the CDE has a linear and a non-linear solution. A radial geometry was assumed, considering a single root with its surface acting as the uptake boundary and the outer boundary being the half distance between neighboring roots, a function of root density. The proposed solute transport model includes active and passive solute uptake and predicts solute concentration as a function of time and distance from the root surface. It also estimates the relative transpiration of the plant, on its turn directly affecting water and solute uptake and related to water and osmotic stress status of the plant. Performed simulations show that the linear and non-linear solutions result in significantly different solute uptake predictions when the soil solute concentration is below a limiting value (Clim). This reduction in uptake at low concentrations may result in a further reduction in the relative transpiration. The contributions of active and passive uptake vary with parameters related to the ion species, the plant, the atmosphere and the soil hydraulic properties. The model showed a good agreement with an analytical model that uses a linear concentration dependent equation as boundary condition for uptake at the root surface. The advantage of the numerical model is it allows simulation of transient solute and water uptake and, therefore, can be used in a wider range of situations. Simulation with different scenarios and comparison with experimental results are needed to verify model performance and possibly suggest improvements. / Uma modificação em um modelo existente de extração de água e transporte de solutos foi realizada com o objetivo de incluir nele a possibilidade de simular a extração de soluto pelas raízes. Uma solução numérica para a equação de convecção-dispersão (ECD), que utiliza um esquema de resolução completamente implícito, foi elaborada e considera o fluxo transiente de água e solutos com uma condição de contorno à superfície da raiz de extração de soluto dependente de sua concentração no solo, baseada na equação de Michaelis- Menten (MM). Uma aproximação linear para a equação de MM foi implementada de tal forma que a ECD tem uma solução linear e outra não-linear. O modelo considera uma raiz singular com geometria radial sendo sua superfície a condição de contorno (limite) de extração e sendo o limite extremo a meia-distância entre raízes vizinhas, função da densidade radicular. O modelo de transporte de soluto proposto inclui extração de soluto ativa e passiva e prediz a concentração de soluto como uma função do tempo e da distância à superfície da raiz, além de estimar a transpiração relativa da planta, que por sua vez afeta a extração de água e solutos e é relacionado com a condição de estresse da planta. Simulações mostram que as soluções linear e não-linear resultam em predições de extração de solutos significativamente diferentes quando a concentração de solutos no solo está abaixo de um valor limitante (Clim). A redução da extração em baixas concentrações pode resultar em uma redução adicional na transpiração relativa. As contribuições ativa e passiva da extração de solutos variam com parâmetros relacionados à espécie de íon, à planta, à atmosfera e às propriedades hidráulicas do solo. O modelo apresentou uma boa concordância com um modelo analítico que aplica uma condição de contorno linear, à superfície da raiz, de extração de solutos dependente da concentração no solo. A vantagem do modelo numérico sobre o analítico é que ele permite simular fluxos transientes de água e solutos, sendo, portanto, possível simular uma maior gama de situações. Se faz necessário simulações com diferentes cenários e comparações com dados experimentais para se verificar a performance do modelo e, possivelmente, sugerir melhorias.

The Solute Carrier (SLC) superfamily is the largest group of membrane-bound transporters, currently with 456 transporters in 52 families. Much remains unknown about the tissue distribution and function of many of these transporters. The aim of this thesis was to characterize select SLCs with emphasis on tissue distribution, cellular localization, and function.       In paper I, we studied the leucine transporter B0AT2 (Slc6a15). Localization of B0AT2 and Slc6a15 in mouse brain was determined using in situ hybridization (ISH) and immunohistochemistry (IHC), localizing it to neurons, epithelial cells, and astrocytes. Furthermore, we observed a lower reduction of food intake in Slc6a15 knockout mice (KO) upon intraperitoneal injections with leucine, suggesting B0AT2 is involved in mediating the anorexigenic effects of leucine.     In paper II, we studied the postnatal, forebrain-specific deletion of Slcz1, belonging to the SLC18 family, in conditional KO mice (cKO). We observed a decreased response to diazepam and a higher neuronal activity in cortex and hippocampus of cKO mice, as well as an impairment in short-term recognition memory. Intracellular expression was found in neurons but not astrocytes with IHC, indicating SLCZ1 is implicated in neuronal regulation of locomotion and memory.    In paper III, we performed the first detailed histological analysis of PAT4, a transporter belonging to the SLC36 family, involved in the activation of mTOR complex 1 on lysosomes. We found abundant Slc36a4 mRNA and PAT4 expression in mouse brain, using ISH and IHC. We used IHC to localize PAT4 to both inhibitory and excitatory neurons and epithelial cells. We also found both intracellular- and plasmalemmal expression and partial colocalization of PAT4 with lysosomal markers.    Lastly, in paper IV, we provided the first tissue mapping of orphan transporter MCT14 (SLC16A14). Using qPCR, we detected moderate to high Slc16a14 mRNA in the central nervous system and kidney. We found widespread Slc16a14 and MCT14 in mouse brain using ISH and IHC. We also found MCT14 to have intracellular and plasmalemmal expression in mainly excitatory but also inhibitory neurons, as well as epithelial cells. We found MCT14 to be most closely related to MCT8, MCT2 and MCT9, suggesting a similar role for this transporter.

Al alloys have been extensively used for producing structural and functional products. It is well known that a grain-refined as cast microstructure generally facilitates high quality finished products in the downstream processing stages. Chemical inoculation by Al-Ti-B grain refiners was widely used in the industry to refine Al alloys. However, the corresponding grain refining mechanism is still under dispute. In this study, the influence of solute elements on the grain refining of Al alloys in the presence of potent TiB2 inoculants was investigated in order to understand the grain refining mechanism of Al alloys by Al-Ti-B grain refiners. Firstly, an effective Al-Ti-B grain refiner, which contains potent TiB2 particles and negligible impurities (particularly Ti), was obtained by a settling experiment. The effectiveness of the grain refiner was verified by its inoculation in commercial purity Al (CP-Al) due to the significantly refined microstructure. Based on its compositional analysis, the grain refiner was found to contain little free Ti (only 600ppm) and other impurities (100ppm Fe, < 100ppm Si), and this refiner was referred to as Al-1.54TiB2. Secondly, with fixed addition of the Al-1.54TiB2 grain refiner, the effect of individual solute elements including Ti, Si, Fe, Sn, Zn, Cu, Mg, Mn, Cr and Zr, and the combined effects of Fe-Si, Fe-Cu and Fe-Ti on the grain structures of high purity Al (HP-Al) were investigated. It was found that, there is no direct correlation between the growth restriction parameter Q and the grain size when a fixed addition of Al-1.54TiB2 is present. The effects of solute elements on the grain structures of a final casting should consider both solidification kinetics and thermodynamic conditions. A theoretical columnar-equiaxed transition (CET) prediction model based on the analysis of a newly-established growth restriction coefficient β, which has considerations on both the thermodynamic and kinetic conditions, is presented for grain structure prediction. Finally, a poisoning (i.e., grain size coarsening) mechanism by Zr or Si addition in Al alloys containing TiB2 particles was studied. It was found that, for Al-Zr samples, a Zr-rich atomic mono-layer exists at the TiB2/Al interface to replace the originally present Al3Ti atomic monolayer. This was suggested to be the reason for Zr poisoning. For Al-Si samples, the Al3Ti atomic monolayer, which originally existed at the TiB2/Al interface, was found to have apparently disappeared, and this was likely to be the reason for Si poisoning.

While restoring hyporheic flowpaths has been cited as a benefit to stream restoration structures, little documentation exists confirming that constructed restoration structures induce hyporheic exchange comparable to natural stream features. This study compares a stream restoration structure (cross-vane) to a natural feature (riffle) concurrently in the same stream reach using time-lapsed electrical resistivity (ER) tomography. Using this hydrogeophysical approach, I am able to quantify hyporheic extent and transport beneath the cross-vane structure and riffle. I interpret from the geophysical data that the cross-vane and natural riffle induced spatially and temporally unique hyporheic extent and transport, and the cross-vane created both spatially larger and temporally longer hyporheic flowpaths than the natural riffle. Tracer from the 4.67-hr injection was detected along flowpaths for 4.6-hrs at the cross-vane and 4.2-hrs at the riffle. The spatial extent of the hyporheic zone at the cross-vane was 12% larger than at the riffle. I compare ER results of this study to vertical fluxes calculated from temperature profiles and conclude significant differences in the interpretation of hyporheic transport from these different field techniques. Results of this study demonstrate a high degree of heterogeneity in transport metrics at both the cross-vane and riffle and significant differences between the hyporheic flowpath networks at the two different features. Our results suggest that restoration structures may be capable of creating sufficient exchange flux and residence times to achieve the same ecological functions as natural features, but engineering of the physical and biogeochemical environment may be necessary to realize those benefits.

Sandy soils are among the least productive soils because of their inability to store adequate water for plant growth. Their high percolation rate not only allows water to move quickly beyond the root zone, but also washes nutrients below the reach of plant roots. High evaporation occurs from the soil surface. Many acres of these soils around the world are left out of crop production. This study is a contribution to bring these soils into production by increasing their ability to hold more water in the root zone. Several promising methods of enhancing these soils were simulated, surface mulch, buried barrier layer, and a combination of both. The effects of varying texture and thickness of these layers and varying evaporative demand were investigated. The impact of such modifications on solute distribution in the soil was also simulated. A simulation model of water and solute transport in layered soils was developed for this purpose. The Richards equation for one-dimensional water transport in unsaturated soils was modified to account for the water jump between the layers. The solute transport equation was also modified by implementing the same theory of water infiltration in layered soil to the solute convective transport. The Crank-Nicolson scheme was used to solve the transport equations with the help of the Newton-Raphson iteration method. The results of the simulation show that the proposed methods increase water content in the sandy soil by up to 45%. The combination of barriers, which decreases leaching and evaporation was the most effective in conserving water. Most of the contribution came from the influence of the mulch layer in suppressing water losses by evaporation. The combination method traps solute in the root zone, and this decreased solute leaching from the soil may limit plant growth in saline soils. / Graduation date: 1993

Geological carbon dioxide (CO₂) storage in deep geological formations can only lead to significant reductions in anthropogenic CO₂ emissions if large amounts of CO₂ can be stored safely. Determining the storage capacity, which is the volume of CO₂ stored safely, is essential to determine the feasibility of geological CO₂ storage. One of the main constraints for the storage capacity is the physical mechanisms of fluid flow in heterogeneous formations, which has not been studied sufficiently. Therefore, I consider two related problems: a) the evolution of injection-induced overpressure that determines the area affected by CO₂ storage and b) the rate of buoyant fluid flow along faults that determines the leakage of CO₂. I use a layered model of a sandstone reservoir embedded in mudrocks to quantify the increase in storage capacity due to dissipation of overpressure into the mudrocks. I use a model of a fault surface with flow barriers to constrain the reduction in the buoyancy-driven leakage flux across the fault. Using the layered model with injection at constant rate, I show that the pressure evolution in the reservoir is controlled by the amount of overpressure dissipated into ambient mudrocks. A main result of this study is that the pressure dissipation in a layered reservoir is controlled by a single dissipation parameter, M, that is identified here for the first time. I also show that lateral pressure propagation in the storage formation follows a power-law governed by M. The quick evaluation of the power-law allows a determination of the uncertainty in the estimate of the storage capacity. To reduce this uncertainty it is important to characterize the petrophysical properties of the mudrocks surrounding the storage reservoir. The uncertainty in mudrock properties due to its extreme heterogeneity or limited data available can cause large variability in these estimates, which emphasizes that careful characterization of mudrock is required for a reliable estimate of the storage capacity. The cessation of the injection operation will reduce overpressure near the injector, but regional scale pressure will continue to diffuse throughout the whole formation. I have been able to show that the maximum radius of the pressure plume in the post-injection period is approximately 3.5 times the radius of the pressure plume at the cessation of injection. Two aquifers can be hydraulically connected by a fault cutting across the intermediate aquitard. If the upper aquifer contains denser fluid, an exchange flow across the fault will develop. The unstable density stratification leads to a fingering pattern with localized zones of upwelling and downwelling along the fault. Due to the small volume of the fault relative to the aquifers, the exchange-flow will quickly approach a quasi steady state. If the permeability of the fault plane is homogeneous, the average number of the quasi-steady plume fingers, (nu), scales with the square root of the Rayleigh number Ra and the exchange flux measured by dimensionless convective flux, the Sherwood number, Sh, is a linear function of Ra. The dispersive flux perpendicular to the flow direction induces the formation of wider fingers and subsequently the less convective flux parallel to the flow direction. In the flow system with larger Ra, even the same increase in transverse dispersivity [alpha]T causes stronger impact of the mechanical dispersion on the vertical exchange flow so that (nu) and Sh reduce more with larger [alpha]T . Both measured characteristics, however, follow the same scaling for the non-dispersive homogeneous case by using a modified Rayleigh number, Ra*, considering the mechanical dispersion. The presence of flow barriers along the fault triggers unsteady exchange flow and subsequently controls the growth of the plume fingers. If the barriers are sufficiently wide to dominate the flow system, they create preferential pathways for exchange flow that determines the distribution of the quasi-steady fingers, and (nu) converges to a constant value. In addition, wider barriers induce substantial lateral spreading and enhance the efficiency of structural trapping, and reduce the exchange rate but still follows a linear relationship function of the effective Rayleigh number, Raeff , defined by the vertical effective permeability. This study is motivated by geological CO₂ storage in brine-saturated aquifer, but the effect of geological heterogeneity is also important in many other geological and engineering applications, in particular the risk assessment of the injection operations or the migration of hydrocarbons in tectonic-driven or hydraulically developed faults in reservoirs. Better understanding of fluid flow in geologically heterogeneous formations will allow more precise estimate of the reservoir capacity as well as more efficient operation of injection or production wells. / text

Solute carriers (SLCs) comprise the largest group of transporters in humans and there are currently 52 SLC families. They are embedded in cellular membranes and transport numerous molecules; defects in many of the genes encoding SLCs have been connected to pathological conditions, and several SLCs are potential drug targets. The SLC38 family has in total eleven members in humans and they encode transporters called SNATs. In paper I and paper II, we reported molecular and functional characterization of Slc38a7 and Slc38a8, two of the previous orphan members in the family which we suggested to be named SNAT7 and SNAT8, respectively. Using in situ hybridization and immunohistochemistry, these transporters showed similar expression pattern and localized to neurons in the brain For functional characterization proteins were overexpressed in X. laevis oocytes and an Uptake Assay and electrophysiological recordings showed preferred transport of L-glutamine, L-histidine, L-alanine, L-asparagine, L-aspartate and L-arginine for SNAT7. A similar pattern was seen for SNAT8 in a slightly different order of affinities. We classified SNAT7 as a system N transporter and SNAT8 as belonging to system A, and suggests that SNAT7 and SNAT8 could play a role in the glutamine/glutamate(GABA) cycle (GGC) in the brain. Furthermore, we studied the vesicular B0AT3 (Slc6a17) transporter in paper III, and the sodium-coupled amino acid transporter B0AT2 (Slc6a15) in paper IV. Tissue expression studies showed similar localization of Slc6a17 and Slc6a15 mRNA using in situ hybridization and real-time PCR. In paper III, vesicular localization of B0AT2 was shown in both excitatory and inhibitory neurons. When challenging the monoaminergic system with drugs both Slc6a17 and Slc6a15 were upregulated. Suggested roles for the transporters are thereby in synaptic remodeling by regulating the availability of free amino acids used as precursors needed in neurotransmitter synthesis. Moreover, in paper IV, immunohistochemistry showed B0AT3 localization to neurons, astrocytes and epithelial cells of the choroid plexus. Leucine injections caused a smaller reduction of food intake as well as higher neuronal activation in the paraventricular hypothalamic nucleus in Slc6a15 KO mice, compared with wild type mice. This suggests B0AT2 involvement in the anorexigenic effects of leucine.