WNT10B mutations in human obesity Christodoulides, C; Scarda, A; Granzotto, M ...
Diabetologia,
04/2006, Letnik:
49, Številka:
4
Journal Article
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Aims/hypothesis Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in ...vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. Subjects and methods We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. Results One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. Conclusions/interpretation These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.
Objective The objective of this study was to assess the prevalence of risk factors for coronary artery disease (CAD) in government employees across India. Methods The study population consisted of ...government employees in different parts of India ({n=10 642 men and n=1966 women; age 20–60 years}) and comprised various ethnic groups living in different environmental conditions. Recruitment was carried out in 20 cities across 14 states, and in one union territory. All selected individuals were subjected to a detailed questionnaire, medical examinations and anthropometric measurements. Blood samples were collected for blood glucose and serum lipid profile estimation, and resting ECG was recorded. Results were analysed using appropriate statistical tools. Results The study revealed that 4.6% of the study population had a family history of premature CAD. The overall prevalence of diabetes was 16% (5.6% diagnosed during the study and the remaining 10.4% already on medication). Hypertension was present in 21% of subjects. The prevalence of dyslipidemia was significantly high, with 45.6% of study subjects having a high total cholesterol/high density lipoprotein ratio. Overall, 78.6% subjects had two or more risk factors for CAD. Conclusions The present study demonstrates a high prevalence of CAD risk factors in the Indian urban population. Therefore, there is an immediate need to initiate measures to raise awareness of these risk factors so that individuals at high risk for future CAD can be managed.
Two opposite parity dipole sequences (DB I and DB II) in 142Eu have been investigated using the Indian National Gamma Array (INGA), and heavy-ion induced fusion-evaporation reaction, 116Cd(31P, 5n) ...at ELab = 148 MeV. The Configurations of these bands are assigned on the basis of tilted axis cranking covariant density functional theory (TAC-CDFT) calculations. The measured B(M1) and B(E2) rates of the DB I and DB II, have been well reproduced within the shears mechanism with the principal axis cranking model (SPAC) calculations leading to the conclusion that these bands have been based on the shears mechanism. The large B(E1) transition rates between DB I and DB II indicate the existence of octupole correlation in 142Eu that has also been corroborated through microscopic multidimensionally-constrained covariant density functional theory (MDC-CDFT) calculations. Thus, the present investigation leads to the novel observation of the presence of octupole correlation between two shears band.
.
The lifetime measurements were done for the transitions of the dipole (
Δ
I
=
1
) bands in
85,86
Sr nuclei using the Doppler Shift Attenuation Method (DSAM). The high-spin states in these nuclei ...were populated in the
76
Ge(
13
C, 4n)
85
Sr and
76
Ge(
13
C, 3n)
86
Sr reactions. The
B
(
M
1) transition rates have been obtained for the states of two positive-parity dipole (
Δ
I
=
1
) bands in the
85
Sr nucleus and one positive-parity dipole (
Δ
I
=
1
) band in the
86
Sr nucleus. The present results on the transition rates are important to know whether these dipole (
Δ
I
=
1
) bands have the signatures of Magnetic Rotation (MR). In order to investigate their magnetic character, the experimental results have been compared with the calculations within the framework of hybrid Tilted-Axis-Cranking (TAC) model. On the basis of the TAC calculations, band 2 of the
85
Sr nucleus is assigned the
π
(
g
9
/
2
)
2
⊗
ν
(
g
9
/
2
)
-
1
configuration and shows the MR character, while for band 3, the
π
(
g
9
/
2
)
2
(
f
5
/
2
)
2
⊗
ν
(
g
9
/
2
)
-
1
configuration is suggested. In the case of
86
Sr nucleus, band 3 has the
π
(
g
9
/
2
)
2
⊗
ν
(
g
9
/
2
)
-
2
configuration below the spin
I
π
=
16
+
and above this spin the
π
(
g
9
/
2
)
2
(
f
5
/
2
)
1
(
p
1
/
2
/
p
3
/
2
)
1
⊗
ν
(
g
9
/
2
)
-
2
configuration plays an important role. The experimental
B
(
M
1) transition rates show a decreasing trend with the increase in spin and are comparable with the TAC calculations before the
I
π
=
16
+
.
A Geant4 simulation code for the Indian National Gamma Array (INGA) consisting of 24 Compton suppressed clover high purity germanium (HPGe) detectors has been developed. The calculated properties in ...the energy range that is of interest for nuclear gamma-ray spectroscopy are spectral distributions for various standard radioactive sources, intrinsic peak efficiencies and peak-to-total (P/T) ratios in various configurations such as singles, add-back and Compton suppressed mode. The principle of operation of the detectors in add-back and Compton suppression mode have been reproduced in the simulation. The reliability of the calculation is checked by comparison with the experimental data for various gamma-ray energies up to 5 MeV. The comparison between simulation results and experimental data demonstrate the need of incorporating the exact geometry of the clover detectors, Anti-Compton Shield and other surrounding materials in the array to explain the detector response to the gamma-ray. Several experimental effects are also investigated. These include the geometrical correction to angular distribution, crosstalk probability and the impact of heavy metal collimators between the target and the array on the P/T ratio.
A major goal of contemporary studies of embryonic development is to understand large sets of regulatory changes that accompany the phenomenon of embryonic induction. The highly resolved sea urchin ...pregastrular endomesoderm-gene regulatory network (EM-GRN) provides a unique framework to study the global regulatory interactions underlying endomesoderm induction. Vegetal micromeres of the sea urchin embryo constitute a classic endomesoderm signaling center, whose potential to induce archenteron formation from presumptive ectoderm was demonstrated almost a century ago. In this work, we ectopically activate the primary mesenchyme cell-GRN (PMC-GRN) that operates in micromere progeny by misexpressing the micromere determinant Pmar1 and identify the responding EM-GRN that is induced in animal blastomeres. Using localized loss-of -function analyses in conjunction with expression of endo16, the molecular definition of micromere-dependent endomesoderm specification, we show that the TGFbeta cytokine, ActivinB, is an essential component of this induction in blastomeres that emit this signal, as well as in cells that respond to it. We report that normal pregastrular endomesoderm specification requires activation of the Pmar1-inducible subset of the EM-GRN by the same cytokine, strongly suggesting that early micromere-mediated endomesoderm specification, which regulates timely gastrulation in the sea urchin embryo, is also ActivinB dependent. This study unexpectedly uncovers the existence of an additional uncharacterized micromere signal to endomesoderm progenitors, significantly revising existing models. In one of the first network-level characterizations of an intercellular inductive phenomenon, we describe an important in vivo model of the requirement of ActivinB signaling in the earliest steps of embryonic endomesoderm progenitor specification.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A sequence of low-energy levels in Ge327846 has been identified with spins and parity of 2+, 3+, 4+, 5+, and 6+. Decays within this band proceed strictly through ΔJ=1 transitions, unlike similar ...sequences in neighboring Ge and Se nuclei. Above the 2+ level, members of this sequence do not decay into the ground-state band. Moreover, the energy staggering of this sequence has the phase that would be expected for a γ-rigid structure. The energies and branching ratios of many of the levels are described well by shell-model calculations. However, the calculated reduced transition probabilities for the ΔJ=2 in-band transitions imply that they should have been observed, in contradiction with the experiment. Within the calculations of Davydov, Filippov, and Rostovsky for rigid-triaxial rotors with γ=30°, there are sequences of higher-spin levels connected by strong ΔJ=1 transitions which decay in the same manner as those observed experimentally, yet are calculated at too high an excitation energy.
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