Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence ...of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2
) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph
) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.
Background and Purpose
Acute hydrocephalus is an early and common complication of aneurysmal subarachnoid hemorrhage (SAH). However, considerably fewer patients develop chronic hydrocephalus ...requiring shunt placement. Our aim was to develop a risk score for early identification of patients with shunt dependency after SAH.
Methods
Two hundred and forty‐two SAH individuals who were treated in our institution between January 2008 and December 2013 and survived the initial impact were retrospectively analyzed. Clinical parameters within 72 h after the ictus were correlated with shunt dependency. Independent predictors were summarized into a new risk score which was validated in a subsequent SAH cohort treated between January and December 2014.
Results
Seventy‐five patients (31%) underwent shunt placement. Of 23 evaluated variables, only the following five showed independent associations with shunt dependency and were subsequently used to establish the Chronic Hydrocephalus Ensuing from SAH Score (CHESS, 0–8 points): Hunt and Hess grade ≥IV (1 point), location of the ruptured aneurysm in the posterior circulation (1 point), acute hydrocephalus (4 points), the presence of intraventricular hemorrhage (1 point) and early cerebral infarction on follow‐up computed tomography scan (1 point). The CHESS showed strong correlation with shunt dependency (P = 0.0007) and could be successfully validated in both internal SAH cohorts tested. Patients scoring ≥6 CHESS points had significantly higher risk of shunt dependency (P < 0.0001) than other patients.
Conclusion
The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies.
Plants utilize sulfate to synthesize primary and secondary sulfur-containing metabolites required for growth and survival in the environment. Sulfate is taken up into roots from the soil and ...distributed to various organs through the functions of membrane-bound sulfate transporters, while it is utilized as the primary substrate for synthesizing sulfur-containing metabolites in the sulfate assimilation pathways. Transporters and enzymes for the assimilative conversion of sulfate are regulated in highly organized manners depending on changes in sulfate supply from the environment and demand for biosynthesis of reduced sulfur compounds in the plant systems. Over the past few decades, the effect of sulfur nutrition on gene expression of sulfate transporters and assimilatory enzymes has been extensively studied with the aim of understanding the full landscape of regulatory networks.
Neuroblastoma is an embryonal tumor with a heterogeneous clinical course. The tumor is presumed to be derived from the neural crest, but the cells of origin remain to be determined. To date, few ...recurrent genetic changes contributing to neuroblastoma formation, such as amplification of the MYCN oncogene and activating mutations of the ALK oncogene, have been identified. The possibility to model neuroblastoma in mice allows investigation of the cell of origin hypothesis in further detail. Here we present the evidence that murine neural crest progenitor cells can give rise to neuroblastoma upon transformation with MYCN or ALK(F1174L). For this purpose we used JoMa1, a multipotent neural crest progenitor cell line, which is kept in a viable and undifferentiated state by a tamoxifen-activated c-Myc transgene (c-MycER(T)). Expression of MYCN or ALK(F1174L), one of the oncogenic ALK variants identified in primary neuroblastomas, enabled these cells to grow independently of c-MycER(T) activity in vitro and caused formation of neuroblastoma-like tumors in vivo in contrast to parental JoMa1 cells and JoMa1 cells-expressing TrkA or GFP. Tumorigenicity was enhanced upon serial transplantation of tumor-derived cells, and tumor cells remained susceptible to the MYC-inhibitor, NBT-272, indicating that cell growth depended on functional MYCN. Our findings support neural crest progenitor cells as the precursor cells of neuroblastoma, and indicate that neuroblastomas arise as their malignant progeny.
The full LEP-1 data set collected with the ALEPH detector at the
Z pole during 1991–1995 is analysed in order to measure the
τ
decay branching fractions. The analysis follows the global method used ...in the published study based on 1991–1993 data, but several improvements are introduced, especially concerning the treatment of photons and
π
0
's. Extensive systematic studies are performed, in order to match the large statistics of the data sample corresponding to over 300
000 measured and identified
τ
decays. Branching fractions are obtained for the two leptonic channels and 11 hadronic channels defined by their respective numbers of charged particles and
π
0
's. Using previously published ALEPH results on final states with charged and neutral kaons, corrections are applied to the hadronic channels to derive branching ratios for exclusive final states without kaons. Thus the analyses of the full LEP-1 ALEPH data are combined to yield a complete description of
τ
decays, encompassing 22 non-strange and 11 strange hadronic modes. Some physics implications of the results are given, in particular related to universality in the leptonic charged weak current, isospin invariance in
a
1
decays, and the separation of vector and axial-vector components of the total hadronic rate. Finally, spectral functions are determined for the dominant hadronic modes and updates are given for several analyses. These include: tests of isospin invariance between the weak charged and electromagnetic hadronic currents, fits of the
ρ
resonance lineshape, and a QCD analysis of the non-strange hadronic decays using spectral moments, yielding the value
α
s
(
m
τ
2
)
=
0.340
±
0
.
005
exp
±
0
.
014
th
. The evolution to the
Z mass scale yields
α
s
(
M
Z
2
)
=
0.1209
±
0.0018
. This value agrees well with the direct determination from the
Z width and provides the most accurate test to date of asymptotic freedom in the QCD gauge theory.
A search for the production and non-standard decay of a Higgs boson, h, into four taus through intermediate pseudoscalars, a, is conducted on 683 pb
−1
of data collected by the ALEPH experiment at ...centre-of-mass energies from 183 to 209 GeV. No excess of events above background is observed, and exclusion limits are placed on the combined production cross section times branching ratio,
. For
m
h
< 107 GeV/
c
2
and 4 <
m
a
< 10 GeV/
c
2
,
ξ
2
> 1 is excluded at the 95% confidence level.
Inclusive particle production in hadronic events taken at the Z resonance with LEP I is reviewed. With approximately 20 million Z decays, the four LEP experiments have studied the fragmentation of ...partons into identified particles. The high statistics allows for a detailed study of this non-perturbative QCD process. In this review the measurements of the four experiments are collected and the momentum spectra are compared to Monte Carlo models. More detailed aspects, such as relative production rates, particle content in gluon jets, particle correlation, etc., are also treated.
Deuteron and anti-deuteron production in Z decays has been observed in the ALEPH experiment at LEP. The production rate of anti-deuterons is measured to be (5.9±1.8±0.5)×10−6 per hadronic Z decay in ...the anti-deuteron momentum range from 0.62 to 1.03 GeV/c. The coalescence parameter B2, which characterizes the likelihood of anti-deuteron production, is measured to be 0.0033±0.0013 GeV2 in Z decays. These measurements indicate that the production of anti-deuterons is suppressed in e+e− collisions compared to that in pp and photoproduction collisions.
The fragmentation of b quarks into B mesons is studied with four million hadronic Z decays collected by the ALEPH experiment during the years 1991–1995. A semi-exclusive reconstruction of
B→ℓ
νD
(★) ...decays is performed, by combining lepton candidates with fully reconstructed
D
(★) mesons while the neutrino energy is estimated from the missing energy of the event.
The mean value of
x
B
wd, the energy of the weakly-decaying B meson normalised to the beam energy, is found to be
〈x
B
wd
〉=0.716±0.006
(
stat)±0.006
(
syst),
using a model-independent method; the corresponding value for the energy of the leading B meson is
〈x
B
L
〉=0.736±0.006
(
stat)±0.006
(
syst)
. The reconstructed spectra are compared with different fragmentation models.
PDF
