Enfin disponible en France, grâce à une étonnante formule Europe, 100% naturelle, vous pouvez maintenant dire stop à vos problèmes d’impuissance et à vos troubles de la virilité. Cette formule révolutionnaire agit comme un véritable achat viagra
naturel. Ses résultats sont immédiats, sans aucun effet secondaire et vos érections sont durables, quelque soit votre âge. Même si vous avez plus de 50 ans !
Aberrant amino acid transport in fibroblasts from children with autism
Elisabeth Fernell , Aristea Karagiannakis , Gunnar Edman ,
Lars Bjerkenstedt , Frits-Axel Wiesel , Nikolaos Venizelos
a Department of Neuropaediatrics, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, SE 171 76 Stockholm, Sweden
b Department of Clinical Medicine, Biomedicine, ¨
c Department of Psychiatry, R& D Section, Danderyd’s Hospital, SE-182 87 Danderyd, Sweden
d Department of Clinical Neuroscience, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
e Department of Neuroscience, Psychiatry, Uller˚aker, Uppsala University Hospital, SE-750 17 Uppsala, Sweden
Received 17 October 2006; received in revised form 20 February 2007; accepted 1 March 2007
Autism is a developmental, cognitive disorder clinically characterized by impaired social interaction, communication and restricted behaviours.
The present study was designed to explore whether an abnormality in transport of tyrosine and/or alanine is present in children with autism. Skinbiopsies were obtained from 11 children with autism (9 boys and 2 girls) fulfilling the DSM-IV diagnostic criteria for autistic disorder and 11healthy male control children. Transport of amino acids tyrosine and alanine across the cell membrane of cultured fibroblasts was studied bythe cluster tray method. The maximal transport capacity, V
max and the affinity constant of the amino acid binding sites, K
m, were determined.
Significantly increased V
max for alanine (p
= 0.014) and increased K
m for tyrosine (p
= 0.007) were found in children with autism. The increasedtransport capacity of alanine across the cell membrane and decreased affinity for transport sites of tyrosine indicates the involvement of two majoramino acid transport systems (L- and A-system) in children with autism. This may influence the transport of several other amino acids across theblood–brain-barrier. The significance of the findings has to be further explored.
2007 Elsevier Ireland Ltd. All rights reserved.
Autism; Amino acid transport; Fibroblasts; Tyrosine; Alanine
Autism is a developmental disorder characterized by severely
tive ability and behaviour becomes evident. This specific form
impaired social interaction, communication and restricted
of autism is referred to as the early regressive type
behaviours. Specific cognitive dysfunctions are linked to this
In line with other developmental disorders several underly-
triad of symptoms The vast majority of the patients have
ing etiologies have been suggested. Prenatal causes of various
an overall low intellectual function with IQs below the normal
kinds dominate However, in most cases, available neuro-
variation. Attention deficits are usually present v-
logical assessments cannot reveal the underlying cause. Autism
ity and stereotypes are common. Other behavioural disturbances,
is a disorder with a strong genetic component Positive
such as self-injuries, tantrums and outbursts may occur, entail-
associations with autism were reported for more than 15 genes
ing a severe clinical picture. Treatment with post-synaptic
dopamine-blockers, i.e. classical neuroleptic drugs, has been
Dopamine (DA) acts as a powerful regulator of different
shown to reduce the symptom level in some patients The
aspects of cognitive functions and is a key neurotransmitter in the
onset of clinical symptoms varies and a considerable number
brain. Several studies have shown its regulatory role for motor
of children develop relatively normally until the age of 18–24
and cognitive/executive functions Already in 1987 Gill-
months. At that time deterioration with respect to communica-
berg and Svennerholm the major DA metabolitehomovanillic acid (HVA) in the cerebrospinal fluid (CSF) inunmedicated children with autism, in children with other devel-opmental disorders and in a healthy comparison group. Children
∗ Corresponding author. Tel.: +46 19 30 10 28; fax: +46 19 30 37 78.
with autism were found to have increased levels of HVA and
the authors suggested that a hyperfunction of the dopaminergic
system in the brain stem and the mesolimbic system could be
0304-3940/$ – see front matter 2007 Elsevier Ireland Ltd. All rights reserved.
E. Fernell et al. / Neuroscience Letters 418 (2007) 82–86
part of the pathogenesis in autism. However, in another study
nia, however, her cognitive problems later became evident, first
of HVA levels in the CSF in children with autism, no signifi-
as a mental retardation, and eventually at the age of 6 years
cant differences were found between children with autism and
autism was diagnosed. (Etiologically a specific syndrome was
controls link between autism, disintegrative disorder, i.e.
autism with late onset (Heller’s syndrome; schizophre-
Eight of the 11 children had undergone a magnetic resonance
nia was proposed by Honjo also discussed by Schieveld
tomography or a computerized tomography with normal results.
In both conditions cognitive dysfunction is an important
The four children with epilepsy were treated with antiepilep-
characteristic. Interestingly, in patients with schizophrenia, we
tics; and one of these children had also received a low dose of
have previously found a connection between tyrosine transport
risperidone. Two other children were treated with a low dose of
and cognitive functioning Tyrosine is the precursor of
risperidone and serotonin reuptake inhibitor, respectively. Rou-
dopamine synthesis and a limitation of its access to the brain
tine plasma amino grams had been performed on all the children
will influence dopamine content and functioning Amino
acids play an important role in brain development and cog-
The Ethics Committee at Karolinska Hospital approved the
nitive functioning, drastically demonstrated in children with
study. The parents were introduced to the study procedure and
phenylketonuria (PKU). In this context it should be of interest
gave informed consent to let their child participate in the study.
to investigate tyrosine transport in children with autism.
Skin biopsies were taken in connection with surgery for
Tyrosine transport is mediated from plasma to brain through
hypospadia in 11 boys between the ages of 1 and 13 years old
membranes mainly via the L-system, named from its func-
(mean 4 years). All were healthy and there was no suspicion of
tion to transport large, neutral, branched and aromatic amino
developmental disorders in any of these children.
acids (LNAA), i.e.
phenylalanine, tyrosine, tryptophan, methio-
All growth media, antibiotics, fetal calf serum and Amnio-
nine, leucine, isoleucine, valine and histidine. The L-system
maxTM were purchased from Gibco Invitrogen cell culture,
is sodium-independent and consists of four isoforms; LAT1,
Sweden. Phosphate buffered saline (PBS) from Statens
LAT2, LAT3 and LAT4 L-system is widely expressed in
Veterin¨armedicinska Anstalt (SVA), Uppsala, Sweden. [U-
the body and occurs in the blood–brain-barrier, kidney and small
14C]-labelled L-tyrosine (specific activity 434 mCi/mmol) and
intestine n fibroblasts only the total tyrosine transport has
[U-14C]-labelled L-alanine (specific activity 128 mCi/mmol)
been studied, without discriminating between the isoforms of
were purchased from Moravek Biochemical Inc., California,
the L-system To a smaller extent, tyrosine is also trans-
U.S.A. Unlabelled L-tyrosine and L-alanine were purchased
ported from plasma to brain by the sodium-dependent A-system
(“A” is an abbreviation for alanine) Three variants of sys-
Fibroblasts were cultured from skin biopsies using Eagle’s
tem A, designed ATA1, ATA2 and ATA3, have been identified
Minimum Essential Medium (EMEM) supplemented with fetal
ransport of short-chain neutral amino acids such as alanine
calf serum (10%, vol/vol), penicillin V (125 U/ml), streptomycin
is mainly mediated by the transport A-system ut also by
(125 g/ml), l-glutamine (2 mmol/l) and Amnio-MaxTM. Stock
L-system TA2 is widely expressed in mammalian tissues
cultures of individual fibroblast stains were cultured in 75 cm2
occurs like the L-system in the blood–brain-barrier
Costar plastic tissue culture flasks in a humidified atmosphere
of 5% CO2 at 37 ◦C. Fibroblast lines were used experimentally
The aim of this study was to test our working hypothesis
that children with autism have changes in amino acid transport
Amino acids transport assays were performed according
mechanisms, based on the profound importance of amino acids
to the fibroblast model rapid measurement of
in brain development and for cognitive functioning.
amino acid flux in adherent intact fibroblast cells. Approxi-
A 2 mm skin punch biopsy was taken after anaesthetizing the
mately 5 × 104 cells were seeded in a 24 multiwell tray (2 cm
mid-forearm under aseptic conditions. The tissue was placed
diameter; Costar Europe Ltd., Costar, NY) and grown to con-
immediately in tubes containing complete culture medium.
fluence in 1.5 ml of MEM for 5 days. The cells were washed
The study group consisted of 11 children with autism,
twice with 1ml phosphate buffered saline (PBS) and directly
according to the DSM-IV criteria 9 boys and 2 girls,
pre-incubated with 1 ml PBS containing 1% glucose for 1 h at
aged 5–11 years (mean 8 years). All were all patients
37 ◦C, 5% CO2 to deplete endogenous amino acids pools. After
at the Neuropaediatric Outpatient Clinic at the Department
removal of the pre-incubation medium, the initial rate of a par-
of Neuropaediatrics, Karolinska University Hospital, Stock-
ticular amino acid uptake was measured during incubation for
holm and had been assessed and diagnosed by experienced
60 s at 37 ◦C in 0.2 ml PBS, containing a constant amount of
neuropaediatric-neuropsychiatric teams. Ten had mental retar-
14C-labelled amino acid (0.2 Curie) and 12 different concen-
dation (U.K. learning disabilities) and one had an IQ in the lower
trations (varying between 0.01 and 1.5 mmol/l for tyrosine and
normal area. Four of the 11 children also had epilepsy, and in at
between 0.02 and 6 mmol/l for alanine) of unlabelled amino
least 2 children without clinical epilepsy, the EEG had revealed
acids. Amino acid transport assay was terminated by rapidly
epileptiform discharges. All boys and one of the girls had an
washing the cells twice with 2 ml of ice-cold PBS. After wash-
uneventful neonatal period and first year of life and clinically
ing, the wells were drained and 230 l of trichloroacetic acid
they were classified as being of the early regressive type. No
(10%, w/v) was added to each well for 20 min at room tempera-
specific disease had earlier been demonstrated. The second girl
ture. Two hundred microlitres of the radioactive soluble amino
had a different clinical picture, starting with muscular hypoto-
acid extract was removed for liquid scintillation counting. The
E. Fernell et al. / Neuroscience Letters 418 (2007) 82–86
trays were drained and the precipitated proteins were dissolved
the other hand the K
(13.9) = 1.05, p
= 0.311] for alanine did
in 1 mol/l NaOH and assayed by the modified Lowry method
not differ significantly between the two groups.
using bovine serum albumin as standard.
max and K
m for tyrosine and alanine for the four chil-
The amino acid kinetic parameters were calculated
dren with autism and epilepsy were compared with those of
from the Lineweaver–Burke plot equation [1/V
0 = (K
the autistic children without epilepsy. There were no significant
]) + (1/V
max)], by using computerized software as described
differences between the groups (data not shown).
previously by Flyckt et al. in 2001. V
0 is the initial transport
Fibroblast cell cultures offer a model for experimental stud-
velocity and [S
] is the transport substrate concentration, V
ies on the transport of amino acids across cell membranes. The
is the maximal uptake rate for the carrier-mediated process
kinetic parameters V
max and K
m were studied, reflecting the
(nmol/min × mg protein) and K
m is the affinity constant (the
maximal transport capacity of tyrosine/alanine and the affin-
concentration at half-saturation; mol/l).
ity of tyrosine/alanine for the binding sites of the transporters,
Each experiment was performed at 12 different concentra-
tions in duplicate in the same incubation for both tyrosine and
The main finding of this study was that fibroblasts from chil-
dren with autism had an elevated V
max for alanine and a higher
The tyrosine transport was studied on two occasions at differ-
m for tyrosine. The higher K
m corresponds with a decreased
ent time points, to diminish cell artefacts that can be caused by
affinity between the transport protein and the substrate tyro-
the condition of the cells, and could influence the low V
sine. The lower affinity for tyrosine indicates that a higher
m tyrosine values. Alanine was analyzed only once since the
concentration of extracellular tyrosine is required to reach the
experiment precision is higher than tyrosine (V
max twice and K
maximal transport capacity, resulting in a decreased competition
five times larger than tyrosine). Differences in V
max and K
between tyrosine and other amino acids. Alanine on the other
tyrosine between autistic and normal children were analyzed by
hand showed a higher transport capacity in this group of chil-
parametric analysis of variance (two-way ANOVA) for repeated
dren with autism, but the K
m did not differ significantly between
measurements (group × measurement).
the two groups. This indicates that fibroblasts from the children
The group differences in alanine transport were analyzed with
with autism in this study group had an elevated expression of
alanine transporting protein. Hence, our main result shows that
The coefficients of variation for the tyrosine determinations
there is a change in the kinetics of tyrosine and alanine transport
measured on two occasions in 11 patients and 11 controls cell
in this study group of children with autism.
lines were 15%, respectively, 16% for V
max and 20% for K
Recently, we have investigated the two major transporters
of tyrosine and alanine (L- and A-systems) in fibroblast from
All variables were summarized by standard descriptive statis-
patients with schizophrenia and controls study pro-
tics (mean and standard deviations). The distributions were
vided evidence that 90% of the total uptake of tyrosine and 65%
scrutinized for deviations from normal. V
max and K
m did not
of alanine were transported through the sodium-independent
deviated from normal distribution. In all analyses, a significance
L-system, whereas 10% of tyrosine and 75% of alanine was
transported by the A-system. Consequently, alanine inhibited
Maximal transport capacity (V
max) and mean affinity of bind-
tyrosine uptake by 65% in fibroblasts in both patients with
ing site (K
m) of tyrosine and alanine in children with autism and
schizophrenia and controls. Therefore, there seems to be a
competition between alanine and tyrosine for transport across
(1, 20) = 2.60, p
= 0.123] for tyrosine did not
differ significantly between the two groups, but the children with
Brain tyrosine is dependent on the influx of this amino acid
autism had a significantly higher K
(1, 20) = 8.90, p
across the blood–brain-barrier. Tyrosine is critical for main-
taining adequate levels of dopamine and therefore of vital
max for alanine was significantly higher [t
(20) = 2.69,
importance for adequate cognitive functions. A major reason for
= 0.014] in the children with autism compared to controls, on
studying tyrosine transport is the association between PKU and
Table 1Kinetic parameters (V
m) of tyrosine and alanine transport in cultured fibroblasts from children with autism and controls
The results are presented as mean (M) and standard deviation (S.D.).V
max, indicates maximal transport capacity (nmol/min × mg protein).K
m, affinity of binding sites for a specific amino acid (mol/l).
a M ± S.D. for tyrosine are based on the average of the two repeated uptake measurements.
E. Fernell et al. / Neuroscience Letters 418 (2007) 82–86
autism. PKU is a well-known developmental disorder, includ-
The number of children with epilepsy in our study is in agree-
ing mental retardation, autism and epilepsy. In PKU there is
ment with the reported frequency of epilepsy in autism, being
a restricted influx of tyrosine into the brain. The biochemical
about one-third According to Tuchman and Rapin
defect is a failure to convert the amino acid phenylalanine to
epilepsy and autism are both heterogeneous clinical disorders
tyrosine due to inadequate functioning of the enzyme, phenylala-
associated with an array of etiologies and pathologies and the
nine hydroxylase. This disorder has been practically eliminated
present evidence suggests that there are common pathophysi-
due to perinatal screening and affected children are given a
ological mechanisms that account for both the autism and the
phenylalanine-restricted diet. Despite treatment lower cognitive
epilepsy. We have no idea whether the proportion of children
functioning, especially with respect to executive functions, has
with both autism and epilepsy in our study group influences our
been demonstrated in patients with PKU These executive
results since the relation of clinical and subclinical epilepsy to
dysfunctions are especially linked to the prefrontal cortex, which
autistic behaviour and early regression is unsettled.
is rich in dopaminergic projection and thus dependent on tyro-
In conclusion, our findings may indicate an elevated access of
sine supply to the brain. The role of tyrosine supplementation
alanine and less availability of tyrosine in the brain, resulting in
in PKU is questionable and Kalsner et al., suggested that the
a lower dopaminergic activity. On the other hand, in vitro
appropriate strategy might be to normalize all brain amino acid
hard to translate to in vivo
situations with reciprocal interactions
involving many complex systems. Our findings demonstrate that
In this study, an aberrant transport of tyrosine and ala-
there may be disturbances in transport mechanisms for amino
nine across the fibroblast cell membrane was demonstrated.
acids, at least at the membrane level. A further exploration of this
We speculate that there might be a corresponding disturbance
research field concerning disturbances of amino acid transport in
of amino acid transport across the blood–brain-barrier. The
children with autism includes molecular investigations, looking
increased transport velocity of alanine across the cell mem-
for polymorphisms in gene loci, and further transport studies,
brane may indicate involvement of the LAT2-transport system
which will hopefully provide more valid answers.
in which there is a competition with tyrosine. LAT2 is oneof the four isoforms that constitute the L-system. LAT2 has
a broader substrate specificity, including tyrosine and alanineand is widely distributed in the body Such competition,
The authors are grateful to Associate Professor Agneta Nor-
due to increased transport of alanine across the blood–brain-
denskj¨old, Department of Pediatric Surgery and Astrid Lindgren
barrier, and accordingly a low tyrosine influx into the brain,
Children’s Hospital for valuable help with material from the
may have different functional consequences. Neurons, and
control children. The study was supported by grants from
particularly dopaminergic neurons, may be more susceptible
S¨allskapet Barnav˚ard, Astrid Lindgren Children’s Hospital,
to disturbances in tyrosine transport resulting in a decreased
Stiftelsen Frimurare Barnhuset in Stockholm (EF), Research
dopamine synthesis in these cells. This could consequently lead
Council (Nr 8318), Magnus Bergvall Foundation, Ingrid Thuring
to compensatory changes in dopaminergic transmission and
and S¨oderstr¨om-K¨oningska Foundation.
Both in schizophrenia and autism the synaptic and connec-
tivity hypotheses have been discussed In a recent report,Bjerkenstedt et al. that the dysfunctional tyro-
 A. Albers, A. Broer, C.A. Wagner, I. Setiawan, P.A. Lang, E.U. Kranz, F.
sine transport from plasma to brain, revealed in patients with
Lang, S. Broer, Na+ transport by the neural glutamine transporter ATA1,
schizophrenia, would affect the dopaminergic pathways and
 G. Allen, E. Courchesne, Attention function and dysfunction in autism,
cause abnormal connectivity, secondary to the aberrant tyrosine
transport. Accordingly, the significance of our present findings,
 American Psychiatric Association, Diagnostic and Statistical Manual of
indicating a decreased affinity for transport sites of tyrosine in
Mental Disorders (DSM-IV), American Psychiatric Press, Washington,
children with autism, might be that such ensuing dopamine dys-
regulation will result in abnormal neural connectivity also in this
 M.K. Belmonte, G. Allen, A. Beckel-Mitchener, L.M. Boulanger, R.A.
Carper, S.J. Webb, Autism and abnormal development of brain connectivity,
There are certain limitations with this study: the patient group
 I.N. Bespalova, J.D. Buxbaum, Disease susceptibility genes for autism,
is small, only 11 children with autism, resulting in a low power of
the statistic analyses. On the other hand, the precision of in vitro
 L. Bjerkenstedt, L. Farde, L. Terenius, G. Edman, N. Venizelos, F.A.
studies is high and fewer patients are needed. Six children with
Wiesel, Support for limited brain availability of tyrosine in patients withschizophrenia, Int. J. Neuropsychopharmacol. 9 (2006) 247–255.
autism were medicated with drugs acting on the CNS. However,
 S. Bodoy, L. Martin, A. Zorzano, M. Palacin, R. Estevez, J. Bertran, Iden-
the present experiments were performed on cells that had grown
tification of LAT4, a novel acid transporter with system L activity, J. Biol.
for several generations in vitro.
It seems unlikely that the results
could be influenced by factors such as the condition of the patient
 S. Danielsson, I.C. Gillberg, E. Billstedt, C. Gillberg, I. Olsson, Epilepsy in
at the time of biopsy or prior medication by drugs acting on the
young adults with autism: a prospective population-based follow-up studyof 120 individuals diagnosed in childhood, Epilepsia 46 (2005) 918–923.
CNS. Rather, the findings observed in the cells from patients
 J.C. Dobson, E. Kushida, M. Williamson, E.G. Friedman, Intellectual per-
with autism may reflect a hereditary trait that can be transmitted
formance of 36 phenylketonuria patients and their nonaffected siblings,
E. Fernell et al. / Neuroscience Letters 418 (2007) 82–86
 L. Flyckt, N. Venizelos, G. Edman, L. Bjerkenstedt, L. Hagenfeldt, F.A.
 Y. Kanai, H. Endou, Functional properties of multispecific amino acid trans-
Wiesel, Aberrant tyrosine transport across the cell membrane in patients
porters and their implications to transporter-mediated toxicity, J. Toxicol.
with schizophrenia, Arch. Gen. Psychiatry 58 (2001) 953–958.
 W.G. Frankle, J. Lerma, M. Laruelle, The synaptic hypothesis of
 B. Mackenzie, J.D. Erickson, Sodium-coupled neutral amino acid (System
schizophrenia, Neuron 39 (2003) 205–216.
N/A) transporters of the SLC38 gene family, Pflugers Arch. 447 (2004)
 G.C. Gazzola, V. Dall’Asta, R. Franchi-Gazzola, M.F. White, The cluster-
tray method for rapid measurement of solute fluxes in adherent cultured
 M. Narayan, S. Srinath, G.M. Anderson, D.B. Meundi, Cerebrospinal fluid
cells, Anal. Biochem. 115 (1981) 368–374.
levels of homovanillic acid and 5-hydroxyindoleacetic acid in autism, Biol.
 R.F. Gazzola, R. Sala, O. Bussolati, R. Visigalli, V. Dall’Asta, V. Ganapathy,
G.C. Gazzola, The adaptive regulation of amino acid transport system A is
 A. Nieoullon, Dopamine and the regulation of cognition and attention,
associated to changes in ATA2 expression, FEBS Lett. 490 (2001) 11–14.
 C. Gillberg, M. Coleman, The Biology of the Autistic Syndromes, third
 E. Olsson, F.A. Wiesel, L. Bjerkenstedt, N. Venizelos, Tyrosine transport
ed., MacKeith Press, Cambridge, UK, 2000.
in fibroblasts from healthy volunteers and patients with schizophrenia,
 C. Gillberg, L. Svennerholm, CSF monoamines in autistic syndromes and
Neurosci. Lett. 393 (2006) 211–215.
other pervasive developmental disorders of early childhood, Br. J. Psychi-
 I. Rapin, Autistic regression and disintegrative disorder: how important the
role of epilepsy? Semin. Pediatr. Neurol. 2 (1995) 278–285.
 L. Hagenfeldt, N. Venizelos, L. Bjerkenstedt, F.A. Wiesel, Decreased tyro-
 J.N. Schieveld, Case reports with a child psychiatric exploration of catato-
sine transport in schizophrenic patients, Life Sci. 41 (1987) 2749–2757.
nia, autism, and delirium, Int. Rev. Neurobiol. 72 (2006) 195–206.
 T. Hatanaka, W. Huang, H. Wang, M. Sugawara, P.D. Prasad, F.H. Leibach,
 S. Shea, A. Turgay, A. Carroll, M. Schulz, H. Orlik, I. Smith, F. Dunbar,
V. Ganapathy, Primary structure, functional characteristics and tissue
Risperidone in the treatment of disruptive behavioral symptoms in children
expression pattern of human ATA2, a subtype of amino acid transport
with autistic and other pervasive developmental disorders, Pediatrics 114
system A, Biochim. Biophys. Acta 1467 (2000) 1–6.
 E.L. Hill, U. Frith, Understanding autism: insights from mind and brain,
 M. Sugawara, T. Nakanishi, Y.J. Fei, W. Huang, M.E. Ganapathy, F.H.
Philos. Trans. R Soc. Lond. B Biol. Sci. 358 (2003) 281–289.
Leibach, V. Ganapathy, Cloning of an amino acid transporter with func-
 S. Honjo, A case in which diagnosis between autism. Heller’s syndrome and
tional characteristics and tissue expression pattern identical to that of
childhood schizophrenia is difficult, Jpn. J. Psychiatry Neurol. 48 (1994)
system A, J. Biol. Chem. 275 (2000) 16473–16477.
 R. Tuchman, I. Rapin, Epilepsy in autism, Lancet Neurol. 1 (2002)
 R. Hyde, P.M. Taylor, H.S. Hundal, Amino acid transporters: roles in
amino acid sensing and signalling in animal cells, Biochem. J. 373 (2003)
 T.H. Wassink, L.M. Brzustowicz, C.W. Bartlett, P. Szatmari, The search
for autism disease genes, Ment. Retard. Dev. Disabil. Res. Rev. 10 (2004)
 L.R. Kalsner, F.J. Rohr, K.A. Strauss, M.S. Korson, H.L. Levy, Tyrosine
supplementation in phenylketonuria: diurnal blood tyrosine levels and pre-
 F.A. Wiesel, G. Edman, L. Flyckt, ˚
sumptive brain influx of tyrosine and other large neutral amino acids, J.
L. Bjerkenstedt, Kinetics of tyrosine transport and cognitive functioning in
schizophrenia, Schizophr. Res. 74 (2005) 81–89.
NEWTOWN PUBLIC SCHOOLS CHECK RUN 06/07/2013 VENDOR NAME ACCOUNT DESCRIPTION DESCRIPTION CI-PA419 iPod Wireless PA System remainder of price. M-319 Califone Belt pack Transmitter. 371201 Total 371202 Total INSTALL BATHROOM DOOR LOCKS / DOOR REPAIRS - HOM 371203 Total 371204 Total LOCAL TRANSPORTATIONFOR SCHOOL YEAR 2012-13ST. ROSE TRANS - 29 BUSES FOR SCHOOL YEAR 2012-
GETTING A YAHOO ID AND ACCESSING/SEARCHING THE ARCHIVES If you have not accessed a Yahoo group before you must be registered with Yahoo and link your registration to the email address you are using in the group. Yahoo requires that you make up a unique name for use of their services (Yahoo ID). NOTE: If you already have a Yahoo ID, skip down to Accessing the Archives . NOTE: You do not nee