The application of NMR chemical shifts is not limited to structural analysis of proteins but they have also been shown to encode information about protein dynamics [20]. The inverse weighted sum of backbone secondary chemical

shifts for Cα, CO, Cβ, N and Hα nuclei defines a so-called Random Coil Index (RCI). Although originally defined for the analysis of globular proteins, applications to IDPs will be feasible given the growing number of experimental studies. Dissolving proteins in anisotropic media selleck compound leads to restricted overall reorientation, thus dipolar coupling interactions no longer average to zero leading to residual dipolar couplings (RDCs) that are experimentally observable in NMR spectra [21].

In IDPs, dynamic averaging of conformations differing in size and shape gives rise to non-zero RDCs. For example, negative 1DNH RDCs are found for segments in which the NH vector is largely oriented perpendicular to the polypeptide chain (extended conformations). Conversely, positive 1DNH values are found for α-helical this website segments [22]. Again, a more sophisticated ensemble approach provides information about specific structural properties such as transient secondary and tertiary structures [23] and [24]. Despite the tremendous success of these applications of RDCs in the past care has to be taken in the case of IDPs and careful control experiments have to be employed to ensure that the conformational ensemble is not significantly perturbed by the anisotropic alignment media. A more comprehensive review of the field is beyond the scope of this perspective article and

can be found elsewhere ([25], and references therein). Undoubtedly the most relevant experimental approach to probe transient long-range contacts in IDPs employs the measurement of paramagnetic relaxation enhancements (PREs) [26]. Since 1H–1H nuclear Overhauser effects (NOEs) 4��8C are characterized by pronounced distance dependence conventional NOESY experiments are not sensitive enough to probe distances beyond approximately 6 Å, particularly, as the effective populations of compact sub-states are generally rather small in IDPs. To study paramagnetic relaxation enhancements the protein under investigation is chemically modified by attaching paramagnetic spin labels at defined positions. Typically, the thiol groups of Cys residues (introduced via site-directed mutagenesis) are used to covalently attach the spin label. It has to be noted that the introduction of paramagnetic spin labels into the protein affects both chemical shifts (pseudo contact shifts, PCS) and/or signal intensities via dipolar relaxation between the unpaired electron and the 1HN and 15N nuclei [27]. Depending on the specific spin label used these effects will be different.

The absorbance was measured using an ELISA reader (Multiskan spectrophotometer EX, Labsystems, Finland) at λ 492 nm. The titre was established as the highest antiserum dilution that produced an absorbance three times greater than that produced by the negative control anti-tetanus serum. The phospholipase A2 Etoposide activity of Tityus spp. venoms was evaluated as described by Price (2007), with some modifications. Microtitre plates were coated with venom samples

(30 μg) combined with buffer (10 mM Triton X-100, 5 mM phosphatidylcholine, 10 mM CaCl2, 0.9% NaCl, 0.03% bromothymol blue; pH 7.5) to a final volume of 200 μL. The activities were determined by measuring the OD at λ 620 nm using a spectrophotometer (Multiskan EX, Labsystems, Finland). As positive and negative controls, venom derived from Crotalus durissus terrificus (10 μg) and PBS was used, respectively. The phospholipase activity was expressed in nanomoles of HCl per minute per mg of venom (nmoles/min/mg) of three independent selleck products experiments. Hyaluronidase activity was measured as described previously by Pukrittayakamee et al. (1988), with slight modifications. Microtitre plates were coated with samples of Tityus spp. venoms (30 μg), 20 μL of the hyaluronic acid substrate (0.5 mg/mL) and acetate buffer (0.2 M

sodium acetate–acetic acid, pH 6.0, containing 0.15 M NaCl) in a final volume of 100 μL. The mixtures were incubated for 15 min at Acetophenone 37 °C. After incubation, 200 μL of CTAB 2.5% in NaOH 2% was added to the samples. The absorbance was measured at λ 405 nm using a spectrophotometer (Multiskan EX, Labsystems, Finland) against a blank containing 100 μL of acetate buffer and 200 μL of CTAB. All of the assays were performed in duplicate. The turbidity-reducing activity was expressed as a percentage of the remaining hyaluronic acid, relative to the absorbance of the well in which venom was omitted. The results were expressed in

units of turbidity reduction (UTR) per mg of venom. The enzymatic activity of the Tityus spp. venoms was determined using the fluorescence resonance energy transfer (FRET) substrate peptide Abz-FLRRV-EDDnp. Venom samples (2 μg of protein) were mixed with 5 μM of FRET substrate, in cold phosphate-buffered saline (PBS). The pH studies were performed in 50 mM sodium citrate buffer (pH 3.0–5.3), 50 mM sodium phosphate buffer (pH 5.2–7.5) and 50 mM Tris–HCl buffer (pH 7.3–10) containing 20 mM NaCl ( Ribeiro-Guimarães et al., 2009). The relative inhibition was determined in parallel using 5 mM PMSF or 5 mM 1,10-phenanthroline, inhibitors of serine- or metalloproteinases, respectively. The stock solutions and the working concentrations of the synthetic inhibitors used in the characterisation of the proteolytic activities exhibited by the venom samples were assessed as described ( Beynon and Bond, 2001).

, 2010; Voragen et al., 1995). Thus, the rheological behavior of CA-HYP at 0.99 g GalA/100 g was evaluated at low pH (2.5–3.0)

with addition of 60 g sucrose/100 g final mixture. The variation of elastic (G′) and viscous (G″) moduli with frequency (0.01–10 Hz) at 25 °C for CA-HYP at low pH and addition of sucrose is shown in Fig. 7. Samples at pH 2.7 and 2.5 showed elastic modulus higher than viscous modulus (G′ > G″) over the frequency range analyzed and G′ was less dependent of frequency than G″, especially at pH 2.5, characterizing a weak gel-like behavior. For the sample at pH 3.0, at lower frequencies G ′> G″ and a cross-over between the moduli occurred at approximately 2.8 Hz. Löfgren, Ceritinib order Walkenström, and Hermansson (2002) also obtained a weak gel with LM pectins (DE 33.5%) at low pH/high sucrose concentration. At 0.75 g pectin concentration/100 g and pH 3.0 with 60% sucrose, in the absence of calcium ions, the gel shows a G′ of 30 Pa and a G″ of 20 Pa at 1 Hz. For the same frequency,

sucrose concentration and pH, CA-HYP at 0.99 GalA/100 g sample showed higher values of G′ and G″, 48 Pa and 43 Pa, respectively. Hot citric-acid extraction appears suitable for the recovery of pectins from cacao pod husks. Slight variation of the uronic acid content (52–62 g/100 g fraction) was observed at the studied levels. However, the extraction yield increased significantly with increasing temperature and time. The experimental yield of pectin in the selected satisfactory conditions (pH 3.0/95 °C/90 min) was found to be in good Anidulafungin (LY303366) agreement with

the predicted check details yield (10.1 g/100 g vs. 9.0 g/100 g, respectively). The pectin obtained is an LM homogalacturonan highly acetylated (DE 40.3%; DA 15.9%) containing rhamnogalacturonan insertions with galactose-rich side chains and showed a non-Newtonian shear-thinning behavior, well fitted by Cross Model. Although gel formation with calcium ions was not observed, the pectin was able to form gels under low pH/high sucrose content, suggesting possible applications as additive in acidic products. The citric-acid-mediated extraction of pectins from the main by-product of cocoa production would not only help to reduce the costs of the production of cocoa products but would also manage the disposal of this waste in an environmental friendly manner through the use of a natural and safe food additive. The authors thank Adonias de Castro Virgens Filho, Miguel Moreno-Ruiz and CEPLAC/CEPEC for supplying the cacao pod husks and CNPq for financial support. “
“Phenylketonuria (PKU) is a disease in which the oxidation of the amino acid phenylalanine (PHE) is impaired due to a deficiency of the PHE hydroxylase enzyme, resulting in several problems in untreated patients, including mental retardation and reduction of life expectancy (Giovannini, Verduci, Salvatici, & Fiori, 2007).

Immediately prior to use, whilst on the surface, the probe was checked by reference to a proprietary standard solution (redox potential of 125 mV, Russel pH Ltd). Redox measurements were taken by inserting the probe into the sediment to a depth of 80 mm. The sediment depth of 80 mm was chosen for four reasons: (1) previous research had indicated that the pre-deployment (baseline) sediment at the reef-site was oxic at this sediment-depth (

Wilding and Sayer, 2002), (2) that achieving very accurate depth penetration by the probe was difficult underwater meaning the errors were proportionately less the greater the sediment-penetration-depth, (3) Dabrafenib that at 80 mm the probe could be left standing, unassisted, in the sediment until the reading had stabilised thus eliminating diver-caused probe shake and (4) as per the recommendation given in Pearson and Stanley (1979) for between-station comparisons. Between measurements, on the same dive, the probe was cleaned by shaking it in the surrounding seawater until a highly positive reading was observed. Where necessary any phytodetrital material was moved to one side prior to inserting the probe. Reported probe readings were adjusted to the hydrogen scale by the addition of 198 mV ( Zobell, 1946) and adjusted for temperature

( SEPA, 2005). Water current speed data were generated over the entire reef site during August 2004 (spring tides, 4.0 m range) using a research vessel-mounted

acoustic Doppler Metalloexopeptidase current profiler (RD Instruments, Mariner, 300 kHz) set to record at 60 Hz. GDC-0199 purchase The survey vessel’s course ran approximately NE–SW, parallel to the shore of Lismore, at a speed of 6–8 knots. The survey consisted of four survey tracks, each approximately 150 m apart. Each survey track ran over, or in close proximity to, the reef groups and each was surveyed 9 times during the 12.5 h survey period (one complete tidal cycle). The current speed data from within 75 m of the centre of each reef group was extracted. ADCP measure current speeds throughout the water column, however, in this case only the current data for the lowest measurable depth (10% of water depth above the seabed) were used to more closely reflect the current environment around the reef modules on the seabed. Outliers were removed by excluding the highest 1% of recorded currents prior to the calculation of median values and the first and third quartiles. The response variable was redox. The distance effect was the main factor of interest. Distances of 0, 1 and 4 m from the reef edge were chosen on the basis of prior observations (Wilding, 2006) and Distance was, therefore, considered fixed. The effect of location (Reef Group) on the distance effect was also of interest. The reef groups were chosen on the basis of their differing characteristics (current exposed or unexposed) and were, therefore, considered fixed.

Performance in a standard battery of neuropsychological tests (Table 1) revealed generally high functioning with no specific functional impairments. He showed above average Wechsler intelligence quotient (IQ) (The Psychological Corporation, 1999) and near-perfect performance on tests of everyday attention (Robertson, 2006), and the Visual Object and Space Perception Battery (Warrington and James, 1991),

with the sole exception of silhouette identification (19/30). Sentence repetition (Spreen and Benton, 1969), performed while the speaker’s face was hidden from view, was perfect and immediate. High resolution magnetic resonance imaging Selumetinib price (MRI) (500 μm3) revealed two lesions. Lesion 1 was located in superior mesencephalon, at the left anterio-medial tip of the subthalamic nucleus (11.5 mm left and 16.8 mm posterior to the anterior commisure). Total lesion volume was 42 mm3. Lesion 2 was located in mid-brainstem within the right dorso-medial pontine nucleus at the level of middle cerebellar peduncle around the exit of the trigeminal nerve (see Fig. 1). These were considered likely to represent small established lacunar infarcts. There was no evidence of an acute ischaemic lesion or VE-822 in vivo microhaemorrhages. Diffusion tensor imaging (DTI) was undertaken using images from healthy subjects, to identify brain regions which are connected to the lesion sites (see Supplementary Methods

S1 and Supplementary Figure 1). Results indicated that lesion 1 had ipsilateral projections predominately into the

motor cortico-striato-pallido-thalamic-cortical relay loop, and a small projection with the Orbito-Frontal relay loop. Cortical projections were consistent with Limbic subthalamic nucleus (STN) (Lambert et al., 2012). Lesion 2 lay along the olivo-collicular pathway (Supplementary Figure 1), with largely ipsilateral projections to inferior colliculus and extending down to the medial territory of the peri-olivary nucleus. There was also a possible involvement of the tectopontine pathway. This second lesion may be associated with the early auditory system. Both regions have been implicated in crossmodal interactions (Halverson and Freeman, 2010; Kolomiets et al., 2001), and in event timing (Teki et al., 2011). Experiment 1 had 10 participants similar in age to PH (59–74 years, mean 65, standard deviation nearly – SD 5). Experiment 2 had 27 neurologically healthy young subjects (18–28 years, mean 22), and included the results from the older age-matched controls. Data from four further participants were excluded, due to poor performance, resulting in implausible estimates of subjective timing >300 msec asynchrony, outside the typical range for multisensory integration (Vatakis et al., 2008; Vatakis and Spence, 2007) and indicative of poor quality data and unreliable function fits. Experiment 3 (testing the Stream–Bounce illusion) had 24 participants aged 18–24, excluding two others who reported no ‘bounce’ illusion.

Freeze-drying

can be defined as the drying of a given substance through its freezing and subsequent removal of associated solvent with the direct sublimation, without passing through the liquid phase. Usually the solvent is water [6]. Freeze-drying process involves three main steps: freezing, primary drying and secondary drying. After freezing the water is removed from the material by sublimation (primary drying). Subsequently, water that remained unfrozen in the first stage is removed by desorption TGF-beta inhibitor under reduced pressure. Freezing is considered one of the most important stages of the process. After freezing the structure, size and shape of the product are fixed. Freezing defines the

size and distribution of ice crystals in the material, and this has an influence on the characteristics of the primary and secondary drying stages [29] and [26]. If the structure of the matrix is altered during freeze-drying it may suffer damage and even result in loss of the product. The thermal treatment annealing can be applied during the freezing stage to bring greater uniformity of size and distribution of ice crystals in the matrix. In annealing, the product is maintained at a specific freezing temperature (above glass transition – Tg – and below the melting temperature of ice crystals in the material) for a period of time to allow the reorganization of ice crystals in the matrix. Then the temperature is taken below the Tg and maintained so that the material does not collapse during primary drying [16], [31] and [1]. selleck chemicals Annealing before freeze-drying [22] could also be useful to facilitate the incorporation of chemical agents into bovine pericardium tissue. In addition,

Maizato et al. 2003 [23] Thalidomide demonstrated that, compared with conventional glutaraldehyde-treated bovine pericardium, freeze-dried pericardium is less cytotoxic, with less residual glutaraldehyde. The work developed by Aimoli et al. 2007 [3] suggests that freeze-drying of bovine pericardium tissue before treatment with chemical substances (crosslinkers) appears to prevent calcification of the matrix. A comparative study between two common ways to obtain dried biomaterials was conducted. Specimens were freeze-dried in two different freeze-dryers: the laboratory freeze-dryer and the pilot freeze-dryer. This study was undertaken in order to study the effect of freeze-drying in the structure of biological tissues (bovine pericardium). Bovine pericardium was collected at a slaughterhouse, cleaned, washed, and stored in glycerol (89% v/v) for preservation. Before use, BP was washed with saline solution (NaCl 0.9% w/v aq.). Specimens were freeze-dried in two different freeze-dryers: the laboratory freeze-dryer (Group A) and the pilot freeze-dryer (Group B).

3% vs 9.2 ± 1.7%, P = .001; Figure 3B). The average number of cells with caspase-3 expression in the treatment group increased significantly compared to that of the control one [(82.6 ± 3.5) × 103 and (21.4 ± 2.3) × 103, respectively; Figure 3A]. All mice were alive during the whole experiment. In the preparatory CP-868596 datasheet study, we observed the tumor slices under the TEM and calculated the mean sizes of gaps between vascular endothelial cells (865 ± 5.2 nm; range, 630-1325 nm) for 20 xenograft tumors. This result indicated that average gap sizes between tumor vascular endothelial cells were larger than our NB mean sizes (586 ± 6.0 nm) in our mouse model.

As the time line in Figure 2 showed, we processed the following experiment and observed that there were no statistical differences in the average weights of mice within four groups on day 0 (P = .76) and day 7 (P = .79). As for tumor sizes, the data indicated no differences among four groups

from day 0 to day 7 during the whole treatment process (P = .98; Figure 4A). Histologic analysis showed that there were no significant differences in the percentage of necrotic areas of samples between treatment (TI and T2) and control groups (C1 and C2; P = .21). At the end of treatment, anti–Her-2 therapy response was investigated by IHC analyses of Her-2 and caspase-3 expression in excised tumors. The data showed that the percentages of Her-2–positive expression in mouse tumors in the two treatment groups

(TI and T2; 54.5% this website and 66.7%) were lower than the control ones (91.2% and 80%, respectively; selleck chemicals Figure 6B). This indicated that there was effective treatment in mouse xenograft models (T1 and T2 groups) and the trastuzumab treatment also induced apoptosis cells in these tumors. Thus, the percentages of caspase-3–positive expression in mouse samples in the two treatment groups (TI and T2) were higher than those of the control groups (C1 and C2; 90.0% and 83.3% vs 66.7% and 70%, respectively; Figure 6A). The ultrasound contrast imaging detected NB signals in in vivo models after 60 minutes from the injection of NB through the mouse tail vein, and this process was carried out under different time points (days 0, 3, 5, and 8; Figure 5A). Then, ultrasound imaging software analyses indicated that the average mean intensities of targeted bubbles in ROIs ( Figure 5B) in the T1 group were significantly higher than those in the other three groups (T2, C1, and C2; P = .001; Figure 4C). However, there were no differences within the three groups (T2, C1, and C2 groups), when one group was compared to other three groups (T2 vs T1 + C1 + C2, P = .74; C1 vs T1 + T2 + C2, P = .51, and C2 vs T1 + T2 + C1, P = .33, respectively). As for peak intensities of intratumor microbubble perfusion, they were also higher in the T1 group than those in the other groups (T2, C1, and C2; P = .00), but there were no differences within T2, C1, and C2 groups (P = .43, .96, and .42, respectively; Figure 4B).

In non-normally distributed variables, logarithmic transformations were applied. Changes between the final and initial evaluations are indicated as delta (Δ). Differences

between groups were analyzed by Student t-test or Mann-Whitney U test for independent samples, according to variable characteristics and distributions. χ2 tests were used for differences in proportion. To analyze differences between basal and final evaluations, paired-samples t test was used. Rho Spearman and Pearson’s correlation coefficient was used to test associations between two types of parameters. SCH727965 Uni- and multivariate logistic regression was used to identify risk factors for the development of MVC or AVC; p ≤0.05 was considered to be significant in all analyses. SPSS Windows v.15 was used for all statistical analyses. A total of 124 patients from the total incident dialysis population were included in the final analysis. Demographic, clinical and biochemical baseline characteristics of the 124 patients are shown in Table 1. Time on dialysis at baseline evaluation was 1.4 ± 1.0 months. No patient had evidence of valve calcification in the initial echocardiographic evaluation. Male gender was over-represented with 68% of the cases, half of the patients were diabetic, 16 (12.9%) had urinary volume <100 mL/day and the proportions in CAPD and APD

were similar. Assignment to a dialysis modality was according to patient preference with orientation by the healthcare team and without Bcl-2 apoptosis pathway the intervention

of the researchers. All 124 patients completed the follow-up period, and the final evaluation was done 12.35 ± 1.02 months after the baseline evaluation. At the end of the follow-up period, valve calcifications were detected in 57 (46%) patients. The aortic valve was calcified in 33 cases (57.8%), the mitral valve in 15 cases (26.3%) and in nine cases (15.8%) both valves were calcified. There was no correlation in the presence or magnitude of calcifications between valves; therefore, for the purposes of analysis, they were considered independently: MVC (42 cases) and AVC (24 cases). Table 2 and Table 3 show the baseline and final Niclosamide values for clinical and biochemical values of patients who developed new MVC or AVC, and they were compared with the 67 patients who did not develop valve calcifications (non-VC). In the baseline evaluation, patients who developed MVC were older, a greater proportion had diabetes, and they had higher values of OPG when compared with patients who did not develop calcifications. After 1 year, this group showed increased values of values of hs-CRP, iPTH and OPG when compared with the patients who did not develop calcifications. In this group, we also observed significant increments in creatinine, albumin, and phosphorus and decreases in GFR between baseline and final values. All other characteristics were similar between baseline and final evaluations and in groups.

The samples of ice cream were produced using a processor (Britania, Curitiba, Brazil) with a churning speed of 815 rpm at −8 °C. The samples were cooled in a freezer (Consul, Whirlpool

S.A., São Paulo, Brazil) at −20 ± 1 °C and stored under this condition until the analysis was carried out. The samples IC4, IC6 and IC8 were prepared following the procedure described above, but without addition of the TG enzyme. The chemical parameters evaluated this website were pH, fat (Soxhlet method), proteins (Kjeldahl method), total sugars (titration), ash and total solids (gravimetric method) (AOAC, 2005). The overrun was evaluated as ((Wt. of mix − Wt. of same vol. of ice cream)/Wt. of same vol. of ice cream) × 100% (Wildmoser, Scheiwiller, &

Windhab, 2004). The fat destabilization of the ice cream samples was evaluated according to the methodology proposed by Goff and Jordan (1989). The ice cream was diluted 500 times with distilled and deionized water and then centrifuged for 5 min at 1200 g (Jaetzki K24, Jena, Germany). The absorbance was measured 10 min later at 540 nm (spectrophotometer model Hitachi U2010, U2010, Tokyo, Japan). Distilled and deionized water was used as the blank. Fat destabilization was calculated as (Amix − Afrozen)/Amix × 100. The melting rate of the ice cream samples was evaluated using the Lee and White (1991) method. The sample (120 g) was placed on a grid with 2 mm hole diameter in a funnel that drained into a graduated cylinder. The sample was allowed to melt in a controlled-temperature selleck room at 25.0 ± 1.0 °C. The weight of the drainage was determined at 10 min intervals and the percentage of melted ice cream was then calculated as a function of time. The rheological measurements of the samples of melted ice cream

were carried out with a Brookfield rotational rheometer with diglyceride a concentric cylinder (model DV-III Ultra, Brookfield Engineering Laboratories, Stoughton, MA, USA) and a ULA spindle. Data were collected using the software 32 Rheocalc® version 2.5 (Brookfield Engineering Laboratories, Inc, Middleboro, MA, USA). The rheometer was thermostatically controlled by a water circulator (model TE-184, TECNAL, São Paulo, Brazil) at 4.0 ± 0.1 °C, and the samples were left to stand for 15 min to ensure stability. The flow behavior of the samples was measured by the linearity of the shear rate from 19.6 to 67.3 s−1 in 20 min and returning to 19.6 s−1 over a further 20 min. The hysteresis of the samples was evaluated from de area between the shear stress/shear rate curves. The Power Law model (Equation (1)) was applied to describe the flow behavior and the consistency index of the samples treated with TG. The apparent viscosity of ice cream samples as a function of time at a constant shear rate was evaluated under a constant shear rate of 20 s−1.

Angesichts der wichtigen physiologischen Funktionen von Mn und der mit einer Mn-Überladung verbundenen Neurotoxizität werden die Resorption, der Transport und die Gewebespiegel von Mn strikt reguliert.

Unter normalen physiologischen Bedingungen wird Mn sowohl beim sich entwickelnden Fetus als auch beim Erwachsenen effizient über die BBB transportiert [14] and [41]. ABT 888 Obwohl der Mn-Transport über die BBB eingehend untersucht wurde, ist noch nicht endgültig geklärt, welche Transportersysteme hauptsächlich dafür verantwortlich sind. Über die letzten 30 Jahre sind jedoch einige Mn-Transportersysteme charakterisiert worden, und zwar sowohl solche, die den aktiven Transport von Mn, als auch solche, die dessen erleichterte Diffusion vermitteln [42], [43] and [44]. Neuere Berichte weisen darauf hin, dass Mn vom divalenten Metallionentransporter 1 (DMT1), vom Transferrin-Rezeptor (TfR), der die Aufnahme von dreiwertigem

Eisen vermittelt, von den divalenten Metall-Bicarbonationen-Symportern Ibrutinib clinical trial ZIP8 und ZIP14, von verschiedenen Calciumkanälen, von der Familie SLC39 (Solute Carrier 39) von Zinktransportern, von PARK9/ATP13A2, vom Magnesiumtransporter hip14 und von den Kanälen bzw. Transportern der Unterfamilie TRPM7 (Transient Receptor Potential Melastatin 7) transportiert werden kann. Die gewebespezifische Expression der einzelnen Mn-Transporter muss zwar noch geklärt werden, es ist jedoch selleck compound wahrscheinlich, dass sämtliche obenerwähnte sowie bisher noch unbekannte Mn-Transporter an der Aufrechterhaltung optimaler Mn-Gewebespiegel beteiligt sind. Darüber hinaus könnte die Aktivität

der obenerwähnten Transporter in Antwort auf Mn-Mangel oder -Überladung durch weitere zelluläre Prozesse kontrolliert werden. Von allen oben aufgelisteten polyvalenten Transportern sind DMT1 und TfR im Hinblick auf ihre Rolle beim Mn-Transport am besten beschrieben [44]. Interessanterweise ist nur ein kleiner Teil des Plasma-Mn an Transferrin (Tf), ein Eisenbindungsprotein, gebunden, während etwa 80 % des Plasma-Mn mit Albumin und Beta1-Globulin assoziiert sind [32]. Der divalente Metallionentransporter 1 (DMT1) ist ein Mitglied der Familie der NRAMP-Proteine (Natural Resistance-associated Macrophage Proteins) und von entscheidender Bedeutung für die Aufrechterhaltung der Homöostase essenzieller Metalle im Gehirn [45], [46] and [47]. Er ist am besten bekannt für seine Rolle bei der Regulation der Fe-Homöostase im gastrointestinalen Lumen [47]. DMT1 ist außerdem bekannt als der divalente Kationentransporter (DCT1), da er divalente Metallionen wie Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+, Pb2+ und Fe2+ über die Plasmamembran ins Zytosol transportiert [45] and [48].