bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes
Authors: Dentice Monica , Luongo Cristina , Huang Stephen , Ambrosio Raffaele , Elefante Antonia , Mirebeau-Prunier Delphine , Zavacki Ann Marie , Fenzi Gianfranco , Grachtchouk Marina , Hutchin Mark , Dlugosz Andrzej A. , Bianco Antonio C. , Missero Caterina , Larsen P. Reed , Salvatore Domenico
Published: August 2007

The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcinomas (BCCs), the most common human malignancy. Type 3 iodothyronine deiodinase (D3), the thyroid hormone-inactivating enzyme, is frequently expressed in proliferating and neoplastic cells, but its role in this context is unknown. Here we show that Shh, through Gli2, directly induces D3 in proliferating keratinocytes and in mouse and human BCCs. We demonstrate that Gli-induced D3 reduces intracellular active thyroid hormone, thus resulting in increased cyclin D1 and keratinocyte proliferation. D3 knockdown caused a 5-fold reduction in the growth of BCC xenografts in nude mice. Shh-induced thyroid hormone degradation via D3 synergizes with the Shh-mediated reduction of the type 2 deiodinase, the thyroxine-activating enzyme, and both effects are reversed by cAMP. This previously unrecognized functional cross-talk between Shh/Gli2 and thyroid hormone in keratinocytes is a pathway by which Shh produces its proliferative effects and offers a potential therapeutic approach to BCC.
Identification of membrane proteins by tandem mass spectrometry of protein ions
Authors: Carroll Joe , Altman Matthew C. , Fearnley Ian M. , Walker John E.
Published: August 2007

The most common way of identifying proteins in proteomic analyses is to use short segments of sequence (“tags”) determined by mass spectrometric analysis of proteolytic fragments. The approach is effective with globular proteins and with membrane proteins with significant polar segments between membrane-spanning α-helices, but it is ineffective with other hydrophobic proteins where protease cleavage sites are either infrequent or absent. By developing methods to purify hydrophobic proteins in organic solvents and by fragmenting ions of these proteins by collision induced dissociation with argon, we have shown that partial sequences of many membrane proteins can be deduced easily by manual inspection. The spectra from small proteolipids (1–4 transmembrane α-helices) are dominated usually by fragment ions arising from internal amide cleavages, from which internal sequences can be obtained, whereas the spectra from larger membrane proteins (5–18 transmembrane α-helices) often contain fragment ions from N- and/or C-terminal parts yielding sequences in those regions. With these techniques, we have, for example, identified an abundant protein of unknown function from inner membranes of mitochondria that to our knowledge has escaped detection in proteomic studies, and we have produced sequences from 10 of 13 proteins encoded in mitochondrial DNA. They include the ND6 subunit of complex I, the last of its 45 subunits to be analyzed. The procedures have the potential to be developed further, for example by using newly introduced methods for protein ion dissociation to induce fragmentation of internal regions of large membrane proteins, which may remain partially folded in the gas phase.
A Skp2 autoinduction loop and restriction point control
Authors: Yung Yuval , Walker Janice L. , Roberts James M. , Assoian Richard K.
Published: August 2007

We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27kip1 (p27), cyclin E–cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27T187A), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus–E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated.
Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia
Authors: Moulding Dale A. , Blundell Michael P. , Spiller David G. , White Michael R.H. , Cory Giles O. , Calle Yolanda , Kempski Helena , Sinclair Jo , Ancliff Phil J. , Kinnon Christine , Jones Gareth E. , Thrasher Adrian J.
Published: August 2007

Specific mutations in the human gene encoding the Wiskott-Aldrich syndrome protein (WASp) that compromise normal auto-inhibition of WASp result in unregulated activation of the actin-related protein 2/3 complex and increased actin polymerizing activity. These activating mutations are associated with an X-linked form of neutropenia with an intrinsic failure of myelopoiesis and an increase in the incidence of cytogenetic abnormalities. To study the underlying mechanisms, active mutant WASpI294T was expressed by gene transfer. This caused enhanced and delocalized actin polymerization throughout the cell, decreased proliferation, and increased apoptosis. Cells became binucleated, suggesting a failure of cytokinesis, and micronuclei were formed, indicative of genomic instability. Live cell imaging demonstrated a delay in mitosis from prometaphase to anaphase and confirmed that multinucleation was a result of aborted cytokinesis. During mitosis, filamentous actin was abnormally localized around the spindle and chromosomes throughout their alignment and separation, and it accumulated within the cleavage furrow around the spindle midzone. These findings reveal a novel mechanism for inhibition of myelopoiesis through defective mitosis and cytokinesis due to hyperactivation and mislocalization of actin polymerization.
Acute Downregulation of ENaC by EGF Involves the PY Motif and Putative ERK Phosphorylation Site
Authors: Falin Rebecca A. , Cotton Calvin U.
Published: August 2007

The epithelial sodium channel (ENaC) is expressed in a variety of tissues, including the renal collecting duct, where it constitutes the rate-limiting step for sodium reabsorption. Liddle's syndrome is caused by gain-of-function mutations in the β and γ subunits of ENaC, resulting in enhanced Na reabsorption and hypertension. Epidermal growth factor (EGF) causes acute inhibition of Na absorption in collecting duct principal cells via an extracellular signal–regulated kinase (ERK)–dependent mechanism. In experiments with primary cultures of collecting duct cells derived from a mouse model of Liddle's disease (β-ENaC truncation), it was found that EGF inhibited short-circuit current (Isc) by 24 ± 5% in wild-type cells but only by 6 ± 3% in homozygous mutant cells. In order to elucidate the role of specific regions of the β-ENaC C terminus, Madin-Darby canine kidney (MDCK) cell lines that express β-ENaC with mutation of the PY motif (P616L), the ERK phosphorylation site (T613A), and C terminus truncation (R564stop) were created using the Phoenix retroviral system. All three mutants exhibited significant attenuation of the EGF-induced inhibition of sodium current. In MDCK cells with wild-type β-ENaC, EGF-induced inhibition of Isc (<30 min) was fully reversed by exposure to an ERK kinase inhibitor and occurred with no change in ENaC surface expression, indicative of an effect on channel open probability (Po). At later times (>30 min), EGF-induced inhibition of Isc was not reversed by an ERK kinase inhibitor and was accompanied by a decrease in ENaC surface expression. Our results are consistent with an ERK-mediated decrease in ENaC open probability and enhanced retrieval of sodium channels from the apical membrane.
Phosducin Regulates the Expression of Transducin βγ Subunits in Rod Photoreceptors and Does Not Contribute to Phototransduction Adaptation
Authors: Krispel Claudia M. , Sokolov Maxim , Chen Yen-Ming , Song Hongman , Herrmann Rolf , Arshavsky Vadim Y. , Burns Marie E.
Published: August 2007

For over a decade, phosducin's interaction with the βγ subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcited rhodopsin. In this study we directly tested this hypothesis by characterizing the dark- and light-adapted response properties of phosducin knockout (Pd−/−) rods. Pd−/− rods were notably less sensitive to light than wild-type (WT) rods. The gain of transduction, as measured by the amplification constant using the Lamb-Pugh model of activation, was 32% lower in Pd−/− rods than in WT rods. This reduced amplification correlated with a 36% reduction in the level of transducin βγ-subunit expression, and thus available heterotrimer in Pd−/− rods. However, commonly studied forms of light adaptation were normal in the absence of phosducin. Thus, phosducin does not appear to contribute to adaptation mechanisms of the outer segment by dynamically controlling heterotrimer availability, but rather is necessary for maintaining normal transducin expression and therefore normal flash sensitivity in rods.
Galois actions and blocks of tame infinitesimal group schemes
Authors: Farnsteiner Rolf , Skowroński Andrzej
Published: August 2007

Given an infinitesimal group

G

\mathcal {G}

, that is defined over an algebra- ically closed field of characteristic

p
≥
3

p \ge 3

, we determine the block structure of the algebra of measures

H
(

G

)

H(\mathcal {G})

in case its principal block

B

0

(

G

)

\mathcal {B}_0(\mathcal {G})

is tame and the height of the factor group

G

/

M

(

G

)

\mathcal {G}/\mathcal {M}(\mathcal {G})

of

G

\mathcal {G}

by its multiplicative center

M

(

G

)

\mathcal {M}(\mathcal {G})

is at least two. Our results yield a complete description of the stable Auslander-Reiten quiver of

H
(

G

)

H(\mathcal {G})

along with a criterion for the domesticity of

H
(

G

)

H(\mathcal {G})

.
Liouville theorems and spectral edge behavior on abelian coverings of compact manifolds
Authors: Kuchment Peter , Pinchover Yehuda
Published: August 2007

The paper describes relations between Liouville type theorems for solutions of a periodic elliptic equation (or a system) on an abelian cover of a compact Riemannian manifold and the structure of the dispersion relation for this equation at the edges of the spectrum. Here one says that the Liouville theorem holds if the space of solutions of any given polynomial growth is finite dimensional. The necessary and sufficient condition for a Liouville type theorem to hold is that the real Fermi surface of the elliptic operator consists of finitely many points (modulo the reciprocal lattice). Thus, such a theorem generically is expected to hold at the edges of the spectrum. The precise description of the spaces of polynomially growing solutions depends upon a ‘homogenized’ constant coefficient operator determined by the analytic structure of the dispersion relation. In most cases, simple explicit formulas are found for the dimensions of the spaces of polynomially growing solutions in terms of the dispersion curves. The role of the base of the covering (in particular its dimension) is rather limited, while the deck group is of the most importance. The results are also established for overdetermined elliptic systems, which in particular leads to Liouville theorems for polynomially growing holomorphic functions on abelian coverings of compact analytic manifolds. Analogous theorems hold for abelian coverings of compact combinatorial or quantum graphs.
Quasilinear elliptic equations with BMO coefficients in Lipschitz domains
Authors: Byun Sun-Sig , Wang Lihe
Published: August 2007

We obtain a global

W

1
,
q

W^{1,q}

estimate for the weak solution to an elliptic partial differential equation of

p
p

-Laplacian type with BMO coefficients in a Lipschitz domain with small Lipschitz constant.
Big Cohen-Macaulay algebras and seeds
Authors: Dietz Geoffrey
Published: August 2007

In this article, we delve into the properties possessed by algebras, which we have termed seeds, that map to big Cohen-Macaulay algebras. We will show that over a complete local domain of positive characteristic any two big Cohen-Macaulay algebras map to a common big Cohen-Macaulay algebra. We will also strengthen Hochster and Huneke’s “weakly functorial" existence result for big Cohen-Macaulay algebras by showing that the seed property is stable under base change between complete local domains of positive characteristic. We also show that every seed over a positive characteristic ring

(
R
,
m
)

(R,m)

maps to a balanced big Cohen-Macaulay

R
R

-algebra that is an absolutely integrally closed,

m
m

-adically separated, quasilocal domain.
Erdös distance problem in vector spaces over finite fields
Authors: Iosevich A. , Rudnev M.
Published: August 2007

We study the Erdös/Falconer distance problem in vector spaces over finite fields. Let

F

q

{\mathbb F}_q

be a finite field with

q
q

elements and take

E
⊂

F

q
d

E \subset {\mathbb F}^d_q

,

d
≥
2

d \ge 2

. We develop a Fourier analytic machinery, analogous to that developed by Mattila in the continuous case, for the study of distance sets in

F

q
d

{\mathbb F}^d_q

to provide estimates for minimum cardinality of the distance set

Δ
(
E
)

\Delta (E)

in terms of the cardinality of

E
E

. Bounds for Gauss and Kloosterman sums play an important role in the proof.
On homeomorphic Bernoulli measures on the Cantor space
Authors: Dougherty Randall , Mauldin R. , Yingst Andrew
Published: August 2007

Let

μ
(
r
)

\mu (r)

be the Bernoulli measure on the Cantor space given as the infinite product of two-point measures with weights

r
r

and

1
−
r

1-r

. It is a long-standing open problem to characterize those

r
r

and

s
s

such that

μ
(
r
)

\mu (r)

and

μ
(
s
)

\mu (s)

are topologically equivalent (i.e., there is a homeomorphism from the Cantor space to itself sending

μ
(
r
)

\mu (r)

to

μ
(
s
)

\mu (s)

). The (possibly) weaker property of

μ
(
r
)

\mu (r)

and

μ
(
s
)

\mu (s)

being continuously reducible to each other is equivalent to a property of

r
r

and

s
s

called binomial equivalence. In this paper we define an algebraic property called “refinability” and show that, if

r
r

and

s
s

are refinable and binomially equivalent, then

μ
(
r
)

\mu (r)

and

μ
(
s
)

\mu (s)

are topologically equivalent. Next we show that refinability is equivalent to a fairly simple algebraic property. Finally, we give a class of examples of binomially equivalent and refinable numbers; in particular, the positive numbers

r
r

and

s
s

such that

s
=

r
2

s = r^2

and

r
=
1
−

s
2

r = 1-s^2

are refinable, so the corresponding measures are topologically equivalent.
Entropy points and applications
Authors: Ye Xiangdong , Zhang Guohua
Published: August 2007

First notions of entropy point and uniform entropy point are introduced using Bowen’s definition of topological entropy. Some basic properties of the notions are discussed. As an application it is shown that for any topological dynamical system there is a countable closed subset whose Bowen entropy is equal to the entropy of the original system. Then notions of C-entropy point are introduced along the line of entropy tuple both in topological and measure-theoretical settings. It is shown that each C-entropy point is an entropy point, and the set of C-entropy points is the union of sets of C-entropy points for all invariant measures.
Heegner points and Mordell-Weil groups of elliptic curves over large fields
Authors: Im Bo-Hae
Published: August 2007

Let

E

/

Q

E/\mathbb {Q}

be an elliptic curve defined over

Q

\mathbb {Q}

of conductor

N
N

and let

Gal
⁡
(

Q

¯

/

Q

)

\operatorname {Gal}(\overline {\mathbb {Q}}/\mathbb {Q})

be the absolute Galois group of an algebraic closure

Q

¯

\overline {\mathbb {Q}}

of

Q

\mathbb {Q}

. For an automorphism

σ
∈
Gal
⁡
(

Q

¯

/

Q

)

\sigma \in \operatorname {Gal}(\overline {\mathbb {Q}}/\mathbb {Q})

, we let

Q

¯

σ

\overline {\mathbb {Q}}^{\sigma }

be the fixed subfield of

Q

¯

\overline {\mathbb {Q}}

under

σ
\sigma

. We prove that for every

σ
∈
Gal
⁡
(

Q

¯

/

Q

)

\sigma \in \operatorname {Gal}(\overline {\mathbb {Q}}/\mathbb {Q})

, the Mordell-Weil group of

E
E

over the maximal Galois extension of

Q

\mathbb {Q}

contained in

Q

¯

σ

\overline {\mathbb {Q}}^{\sigma }

has infinite rank, so the rank of

E
(

Q

¯

σ

)

E(\overline {\mathbb {Q}}^{\sigma })

is infinite. Our approach uses the modularity of

E

/

Q

E/\mathbb {Q}

and a collection of algebraic points on

E
E

– the so-called Heegner points – arising from the theory of complex multiplication. In particular, we show that for some integer

r
r

and for a prime

p
p

prime to

r
N

rN

, the rank of

E
E

over all the ring class fields of a conductor of the form

r

p
n

rp^n

is unbounded, as

n
n

goes to infinity.
A review of feature selection techniques in bioinformatics
Authors: Saeys Yvan , Inza Iñaki , Larrañaga Pedro
Published: August 2007

Feature selection techniques have become an apparent need in many bioinformatics applications. In addition to the large pool of techniques that have already been developed in the machine learning and data mining fields, specific applications in bioinformatics have led to a wealth of newly proposed techniques.

In this article, we make the interested reader aware of the possibilities of feature selection, providing a basic taxonomy of feature selection techniques, and discussing their use, variety and potential in a number of both common as well as upcoming bioinformatics applications.

Contact:  yvan.saeys@psb.ugent.be

Supplementary information:  http://bioinformatics.psb.ugent.be/supplementary_data/yvsae/fsreview
LICORN: learning cooperative regulation networks from gene expression data
Authors: Elati Mohamed , Neuvial Pierre , Bolotin-Fukuhara Monique , Barillot Emmanuel , Radvanyi François , Rouveirol Céline
Published: August 2007

Motivation: One of the most challenging tasks in the post-genomic era is the reconstruction of transcriptional regulation networks. The goal is to identify, for each gene expressed in a particular cellular context, the regulators affecting its transcription, and the co-ordination of several regulators in specific types of regulation. DNA microarrays can be used to investigate relationships between regulators and their target genes, through simultaneous observations of their RNA levels.

Results: We propose a data mining system for inferring transcriptional regulation relationships from RNA expression values. This system is particularly suitable for the detection of cooperative transcriptional regulation. We model regulatory relationships as labelled two-layer gene regulatory networks, and describe a method for the efficient learning of these bipartite networks from discretized expression data sets. We also evaluate the statistical significance of such inferred networks and validate our methods on two public yeast expression data sets.

Availability:  http://www.lri.fr/~elati/licorn.html

Contact:  mohamed.elati@curie.fr

Supplementary information: Supplementary data are available at Bioinformatics online.
Current status and temporal trends in stocks of European eel in England and Wales
Authors: Bark A. , Williams B. , Knights B.
Published: August 2007

Bark, A., Williams, B., and Knights, B. 2007. Current status and temporal trends in stocks of European eel in England and Wales. – ICES Journal of Marine Science, 64: –. An extensive 4-year programme of catchment surveys, data collection, and model development for eels was undertaken to establish the status of the stocks in England and Wales, so that appropriate management action can be taken. Nine test catchments representing different geographical areas and catchment types were studied, covering 14 rivers, two estuaries, and a fresh-water lagoon. Data were collected via electric fishing, fykenetting, fixed eel racks, and elver traps. In all, 13 500 eels were caught, weighed, and measured, and the sex and age of a subsample of 1400 determined. Despite declining recruitment, eel stocks in some, perhaps many, west coast rivers are probably still at or near to carrying capacity, with male-dominated populations. In other rivers, particularly those towards the southeast of England, current and historical data indicate declining female-dominated stocks. For rivers where recruitment is not limiting, there appears to be a direct relationship between the standing stock of eels and the mean nitrate level. This relationship potentially facilitates the application of a biomass-based biological reference point for eels for application to individual catchments. The data also suggest that it may be possible to develop reference points based on mean eel length or sex ratio.
Eels: contaminant cocktails pinpointing environmental contamination
Authors: Belpaire C. , Goemans G.
Published: August 2007

Belpaire, C., and Goemans, G. 2007. Eels: contaminant cocktails pinpointing environmental contamination. – ICES Journal of Marine Science, 64: –. There is growing concern that insufficient somatic and health conditions of silver European eels (Anguilla anguilla) emigrating from European waters to oceanic spawning areas might be a key causative factor in the decline of the stock. One factor that could contribute to deterioration in the status of eels is high contaminant accumulation in their body. Contaminants may affect lipid metabolism and result in lower energy stores. A high body burden of contaminants and low energy stores might be responsible for failure of migration and/or impairment of successful reproduction. During a 12-year study on a relatively small area within the river basins of IJzer, Scheldt, and Meuse (ca. 13 500 km2), 2613 eels were sampled covering a dense monitoring network of 357 stations. Eels were analysed for ca. 100 chemicals. These included PCBs, organochlorine pesticides, heavy metals, brominated flame retardants, volatile organic pollutants (VOCs), endocrine disruptors, dioxins, perfluorooctane sulphonic acids (PFOSs), metallothioneins, and polycyclic aromatic compounds. This series represents only a very small fraction (<0.5%) of the >30 000 chemicals currently marketed and used in Europe. The biomonitoring value of eels as a tool for monitoring environmental contamination is illustrated. Two major conclusions were drawn: (i) the eel is a highly suitable biomonitor for environmental contaminants, for both local and international purposes, e.g. to evaluate the chemical status for the Water Framework Directive, and (ii) dependent on the degree of pollution in their habitat, the levels of certain contaminants reported in yellow eels can be high, and might affect their potential for reproduction.
The feasibility of escape mechanisms in conical snow crab traps
Authors: Winger Paul D. , Walsh Philip J.
Published: August 2007

Winger, P. D., and Walsh, P. J. 2007. The feasibility of escape mechanisms in conical snow crab traps. – ICES Journal of Marine Science, 64: 1587–1591. Laboratory observations and morphometric measurements of snow crab (Chionoecetes opilio) were conducted to examine the feasibility of incorporating rigid escape mechanisms into conical snow crab traps to improve trap selectivity. Under laboratory conditions, undersized adolescent male snow crab (≤94 mm carapace width) were capable of detecting, approaching, and interacting with escape mechanisms, and the location of the mechanisms was important in determining the likelihood of escape success. Escape mechanisms mounted low on the exterior wall of the trap received more than three times the number of penetration attempts than those mounted higher, although successful escape rates were very low. There was no difference in behaviour or escape success between traditional mesh traps and experimental wire (Aquamesh®) traps fitted with escape mechanisms. Morphometric measurements suggest that an escape diameter of 95 mm would optimize the egress of small crab and prevent the loss of legal-sized crab.
The Efficacy of Treatment of Different Intervention Programs for Patellofemoral Pain Syndrome–A Single Blinded Randomized Clinical Trial. Pilot Study
Authors: Avraham Feazadeh , Aviv Saposhnik , Ya'akobi Pnina , Faran Hava , Fisher Zilla , Goldman Yael , Neeman Guy , Carmeli Eli
Published: August 2007

Patello-femoral pain syndrome (PFPS) is a common knee joint disability. The integration of hip soft tissue regimens are not always emphasized, although current literature implies that there is a significant relationship between the two and there is a lack of randomized clinical trials to substantiate this relationship in clinical practice. A randomized controlled assessor blinded trial was designed to explore different rehabilitation programs related to PFPS. The study was conducted at RAZIEL institute of physical therapy, Netania, Israel with a total of 30 consecutive patients (mean age 35y), diagnosed with PFPS. All patients were randomly allocated into 3 groups. Group I conventional knee rehabilitation program. Included quadriceps strengthening and Trans Electric Neuromuscular Stimulation (TENS). Group II hip oriented rehabilitation program. included stretching, Hip external rotators strengthening and TENS. Group III a combination of the two above programs. Pain and function were documented on initial of the program and again 3 weeks later, on the completion. Pain was assessed by a numeric visual analogue scale (VAS); function was assessed by Patello-femoral joint evaluation scale (PFJES) (0-100 points). At end of trial, all groups showed significant improvements in VAS and PFJES (p<0.0001); these improvements did not vary significantly between the 3 groups. The conclusions were that the explored different rehabilitation programs showed a similar beneficial effect.
Effects of Biphenyldimethyl-dicarboxylate Administration Alone or Combined with Silymarin in the CCL4Model of Liver Fibrosis in Rats
Authors: Abdel-Salam Omar M. E. , Sleem Amany A. , Morsy Fatma A.
Published: August 2007

The effect of biphenyldimethyldicarboxylate (DDB), a synthetic compound, in use for the treatment of chronic hepatitis was studied on hepatic injury caused in rats by administration of carbon tetrachloride (CCl4). Starting at time of administration of the first dose of CCl4, rats received DDB at four dose levels (3, 15, 75 or 375 mg/kg), silymarin (22 mg/kg), a combination of DDB (75 mg/kg) and silymarin (22 mg/kg) or saline (control) once orally daily for 30 days. The administration of DDB in CCl4-treated rats at 75 or 375 mg/kg resulted in 61.2-76.2% decrease in alanine aminotransferase (ALT) and 46.9-60.8% decrease in aspartate aminotransferase (AST), respectively compared with the CCl4control group. Silymarin treatment resulted in 34.6 and 30% decrease in ALT and AST, while DDB (75 mg/kg) combined with silymarin (22 mg/kg) resulted in 58.2 and 31% decrease in ALT and AST, respectively. Serum creatinine increased by 50% by DDB at 375 mg/kg. After treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin, the development of liver necrosis and fibrosis caused by CCl4was markedly reduced, while after DDB combined with silymarin no DNA aneuploid cells could be observed. The decrease in glycogen and protein contents in hepatocytes caused by CCl4was markedly prevented by co-treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin. It is concluded that in the model of hepatic injury caused by chronic administration of CCl4in rats, the synthetic compound DDB, limits hepatocellular injury and exerts antifibrotic effect. Better improvement in protein, DNA, mucopolysaccharide content was seen after both DDB and silymarin compared to DDB alone. It is suggested, therefore, that DDB alone or in combination with silymarin might prove of benefit in the therapy of chronic liver disease. Monitoring of kidney functions in patients taking DDB is warranted.
Orexitropic Signaling Proteins in Obese Children
Authors: Saranac Ljiljana , Bjelakovic Bojko , Stamenkovic Hristina , Kamenov Borislav
Published: August 2007

Adipose tissue is not only the main organ for energy storage, but it also has endocrine properties, producing “adipokines” responsible for energy homeostasis, insulin sensitivity, and inflammation. Leptin, produced by adipocytes, is the key hormone in appetite regulation and suppression of orexigenic, hypothalamic neuropeptide Y (NPY). We wanted to establish and compare levels of leptin and NPY in different obesity types in childhood, and to investigate their correlations with auxological parameters. Twenty-one obese children (seven girls and 14 boys), divided into two groups, were compared with 14 controls. The mean age of the study group was 10.81 ± 3.69 years and the mean puberty stage was 2.21. The mean body mass index (BMI) was 32.80 kg/m2(range 23.30– 47.02) and the mean overweight 30.73 kg (range 8.00–74.00). The mean leptin level was higher in boys and in the group with central obesity, but was not significant. Leptin/NPY ratio and leptin/BMI ratio was also higher in the central obesity group and there was a more significant difference compared with controls. We found significant correlation of the leptin level with body mass (BM), body mass excess (BME), and BMI (p < 0.05). The mean leptin level in obese children was very high (36.39 ng/ml). Leptin and NPY levels showed inverse values in two different obesity types. Results are suggestive for leptin resistance rather than leptin deficiency in our group of obese children. Orexitropic signaling proteins correlated significantly with auxological parameters. Determination of the leptin and NPY concentrations provided evidence that obesity represents disease with neuroendocrine dysfunction and high leptin/NPY ratio, which could be a useful marker for central obesity.
Flavonoids Are Differentially Taken Up and Transported Long Distances in Arabidopsis
Authors: Buer Charles S. , Muday Gloria K. , Djordjevic Michael A.
Published: August 2007

Flavonoids are synthesized in response to developmental and environmental signals and perform many functions in plants. Arabidopsis (Arabidopsis thaliana) roots grown in complete darkness do not accumulate flavonoids since the expression of genes encoding enzymes of flavonoid biosynthesis is light dependent. Yet, flavonoids accumulate in root tips of plants with light-grown shoots and light-shielded roots, consistent with shoot-to-root flavonoid movement. Using fluorescence microscopy, a selective flavonoid stain, and localized aglycone application to transparent testa mutants, we showed that flavonoids accumulated in tissues distal to the application site, indicating uptake and movement systems. This was confirmed by time-course fluorescence experiments and high-performance liquid chromatography. Flavonoid applications to root tips resulted in basipetal movement in epidermal layers, with subsequent fluorescence detected 1 cm from application sites after 1 h. Flavonoid application to midroot or cotyledons showed movement of flavonoids toward the root tip mainly in vascular tissue. Naringenin, dihydrokaempferol, and dihydroquercetin were taken up at the root tip, midroot, or cotyledons and traveled long distances via cell-to-cell movement to distal tissues, followed by conversion to quercetin and kaempferol. In contrast, kaempferol and quercetin were only taken up at the root tip. Using ATP-binding cassette (ABC) transporter and H+-ATPase inhibitors suggested that a multidrug resistance-associated protein ABCC transporter facilitated flavonoid movement away from the application site.
Reduced Carbon Availability to Bacteroids and Elevated Ureides in Nodules, But Not in Shoots, Are Involved in the Nitrogen Fixation Response to Early Drought in Soybean
Authors: Ladrera Rubén , Marino Daniel , Larrainzar Estíbaliz , González Esther M. , Arrese-Igor Cesar
Published: August 2007

Nitrogen fixation (NF) in soybean (Glycine max L. Merr.) is highly sensitive to soil drying. This sensitivity has been related to an accumulation of nitrogen compounds, either in shoots or in nodules, and a nodular carbon flux shortage under drought. To assess the relative importance of carbon and nitrogen status on NF regulation, the responses to the early stages of drought were monitored with two soybean cultivars with known contrasting tolerance to drought. In the sensitive cultivar (‘Biloxi’), NF inhibition occurred earlier and was more dramatic than in the tolerant cultivar (‘Jackson’). The carbon flux to bacteroids was also more affected in ‘Biloxi’ than in ‘Jackson’, due to an earlier inhibition of sucrose synthase activity and a larger decrease of malate concentration in the former. Drought provoked ureide accumulation in nodules of both cultivars, but this accumulation was higher and occurred earlier in ‘Biloxi’. However, at this early stage of drought, there was no accumulation of ureides in the leaves of either cultivar. These results indicate that a combination of both reduced carbon flux and nitrogen accumulation in nodules, but not in shoots, is involved in the inhibition of NF in soybean under early drought.
A Novel Image-Analysis Technique for Kinematic Study of Growth and Curvature
Authors: Basu Paramita , Pal Anupam , Lynch Jonathan P. , Brown Kathleen M.
Published: August 2007

Kinematic analysis has provided important insights into the biology of growth by revealing the distribution of expansion within growing organs. Modern methods of kinematic analysis have made use of new image-tracking algorithms and computer-assisted evaluation, but these methods have yet to be adapted for examination of growth in a variety of plant species or for analysis of graviresponse. Therefore, a new image-analysis program, KineRoot, was developed to study spatio-temporal patterns of growth and curvature of roots. Graphite particles sprinkled on the roots create random patterns that can be followed by image analysis. KineRoot tracks the displacement of patterns created by the graphite particles over space and time using three search algorithms. Following pattern tracking, the edges of the roots are identified automatically by an edge detection algorithm that provides root diameter and root midline. Local growth rate of the root is measured by projecting the tracked points on the midline. From the shape of the root midline, root curvature is calculated. By combining curvature measurement with root diameter, the differential growth ratio between the greater and lesser curvature edges of a bending root is calculated. KineRoot is capable of analyzing a large number of images to generate local root growth and root curvature data over several hours, permitting kinematic analysis of growth and gravitropic responses for a variety of root types.
Optimizing the Distribution of Resources between Enzymes of Carbon Metabolism Can Dramatically Increase Photosynthetic Rate: A Numerical Simulation Using an Evolutionary Algorithm
Authors: Zhu Xin-Guang , de Sturler Eric , Long Stephen P.
Published: August 2007

The distribution of resources between enzymes of photosynthetic carbon metabolism might be assumed to have been optimized by natural selection. However, natural selection for survival and fecundity does not necessarily select for maximal photosynthetic productivity. Further, the concentration of a key substrate, atmospheric CO2, has changed more over the past 100 years than the past 25 million years, with the likelihood that natural selection has had inadequate time to reoptimize resource partitioning for this change. Could photosynthetic rate be increased by altered partitioning of resources among the enzymes of carbon metabolism? This question is addressed using an “evolutionary” algorithm to progressively search for multiple alterations in partitioning that increase photosynthetic rate. To do this, we extended existing metabolic models of C3 photosynthesis by including the photorespiratory pathway (PCOP) and metabolism to starch and sucrose to develop a complete dynamic model of photosynthetic carbon metabolism. The model consists of linked differential equations, each representing the change of concentration of one metabolite. Initial concentrations of metabolites and maximal activities of enzymes were extracted from the literature. The dynamics of CO2 fixation and metabolite concentrations were realistically simulated by numerical integration, such that the model could mimic well-established physiological phenomena. For example, a realistic steady-state rate of CO2 uptake was attained and then reattained after perturbing O2 concentration. Using an evolutionary algorithm, partitioning of a fixed total amount of protein-nitrogen between enzymes was allowed to vary. The individual with the higher light-saturated photosynthetic rate was selected and used to seed the next generation. After 1,500 generations, photosynthesis was increased substantially. This suggests that the “typical” partitioning in C3 leaves might be suboptimal for maximizing the light-saturated rate of photosynthesis. An overinvestment in PCOP enzymes and underinvestment in Rubisco, sedoheptulose-1,7-bisphosphatase, and fructose-1,6-bisphosphate aldolase were indicated. Increase in sink capacity, such as increase in ADP-glucose pyrophosphorylase, was also indicated to lead to increased CO2 uptake rate. These results suggest that manipulation of partitioning could greatly increase carbon gain without any increase in the total protein-nitrogen investment in the apparatus for photosynthetic carbon metabolism.
Regulation of One-Carbon Metabolism in Arabidopsis: The N-Terminal Regulatory Domain of Cystathionine γ-Synthase Is Cleaved in Response to Folate Starvation
Authors: Loizeau Karen , Gambonnet Bernadette , Zhang Guo-Fang , Curien Gilles , Jabrin Samuel , Van Der Straeten Dominique , Lambert Willy E. , Rébeillé Fabrice , Ravanel Stéphane
Published: August 2007

In all organisms, control of folate homeostasis is of vital importance to sustain the demand for one-carbon (C1) units that are essential in major metabolic pathways. In this study we induced folate deficiency in Arabidopsis (Arabidopsis thaliana) cells by using two antifolate inhibitors. This treatment triggered a rapid and important decrease in the pool of folates with significant modification in the distribution of C1-substituted folate coenzymes, suggesting an adaptive response to favor a preferential shuttling of the flux of C1 units to the synthesis of nucleotides over the synthesis of methionine (Met). Metabolic profiling of folate-deficient cells indicated important perturbation of the activated methyl cycle because of the impairment of Met synthases that are deprived of their substrate 5-methyl-tetrahydrofolate. Intriguingly, S-adenosyl-Met and Met pools declined during the initial period of folate starvation but were further restored to typical levels. Reestablishment of Met and S-adenosyl-Met homeostasis was concomitant with a previously unknown posttranslational modification that consists in the removal of 92 amino acids at the N terminus of cystathionine γ-synthase (CGS), the first specific enzyme for Met synthesis. Rescue experiments and analysis of different stresses indicated that CGS processing is specifically associated with perturbation of the folates pool. Also, CGS processing involves chloroplastic serine-type proteases that are expressed in various plant species subjected to folate starvation. We suggest that a metabolic effector, to date unidentified, can modulate CGS activity in vivo through an interaction with the N-terminal domain of the enzyme and that removal of this domain can suppress this regulation.
Reverse Genetics of Floral Scent: Application of Tobacco Rattle Virus-Based Gene Silencing in Petunia
Authors: Spitzer Ben , Zvi Michal Moyal Ben , Ovadis Marianna , Marhevka Elena , Barkai Oren , Edelbaum Orit , Marton Ira , Masci Tania , Alon Michal , Morin Shai , Rogachev Ilana , Aharoni Asaph , Vainstein Alexander
Published: August 2007

Floral fragrance is responsible for attracting pollinators as well as repelling pathogens and pests. As such, it is of immense biological importance. Molecular dissection of the mechanisms underlying scent production would benefit from the use of model plant systems with big floral organs that generate an array of volatiles and that are amenable to methods of forward and reverse genetics. One candidate is petunia (Petunia hybrida), which has emerged as a convenient model system, and both RNAi and overexpression approaches using transgenes have been harnessed for the study of floral volatiles. Virus-induced gene silencing (VIGS) is characterized by a simple inoculation procedure and rapid results relative to transgenesis. Here, we demonstrate the applicability of the tobacco rattle virus-based VIGS system to studies of floral scent. Suppression of the anthocyanin pathway via chalcone synthase silencing was used as a reporter, allowing easy visual identification of anthocyaninless silenced flowers/tissues with no effect on the level of volatile emissions. Use of tobacco rattle virus constructs containing target genes involved in phenylpropanoid volatile production, fused to the chalcone synthase reporter, allowed simple identification of flowers with suppressed activity of the target genes. The applicability of VIGS was exemplified with genes encoding S-adenosyl-l-methionine:benzoic acid/salicylic acid carboxyl methyltransferase, phenylacetaldehyde synthase, and the myb transcription factor ODORANT1. Because this high-throughput reverse-genetics approach was applicable to both structural and regulatory genes responsible for volatile production, it is expected to be highly instrumental for large-scale scanning and functional characterization of novel scent genes.
Ethylene Is One of the Key Elements for Cell Death and Defense Response Control in the Arabidopsis Lesion Mimic Mutant vad1
Authors: Bouchez Olivier , Huard Carine , Lorrain Séverine , Roby Dominique , Balagué Claudine
Published: August 2007

Although ethylene is involved in the complex cross talk of signaling pathways regulating plant defense responses to microbial attack, its functions remain to be elucidated. The lesion mimic mutant vad1-1 (for vascular associated death), which exhibits the light-conditional appearance of propagative hypersensitive response-like lesions along the vascular system, is a good model for studying the role of ethylene in programmed cell death and defense. Here, we demonstrate that expression of genes associated with ethylene synthesis and signaling is enhanced in vad1-1 under lesion-promoting conditions and after plant-pathogen interaction. Analyses of the progeny from crosses between vad1-1 plants and either 35S∷ERF1 transgenic plants or ein2-1, ein3-1, ein4-1, ctr1-1, or eto2-1 mutants revealed that the vad1-1 cell death and defense phenotypes are dependent on ethylene biosynthesis and signaling. In contrast, whereas vad1-1-dependent increased resistance was abolished by ein2, ein3, and ein4 mutations, positive regulation of ethylene biosynthesis (eto2-1) or ethylene responses (35S∷ERF1) did not exacerbate this phenotype. In addition, VAD1 expression in response to a hypersensitive response-inducing bacterial pathogen is dependent on ethylene perception and signaling. These results, together with previous data, suggest that VAD1 could act as an integrative node in hormonal signaling, with ethylene acting in concert with salicylic acid as a positive regulator of cell death propagation.
TRBO: A High-Efficiency Tobacco Mosaic Virus RNA-Based Overexpression Vector
Authors: Lindbo John A.
Published: August 2007

Transient expression is a rapid, useful approach for producing proteins of interest in plants. Tobacco mosaic virus (TMV)-based transient expression vectors can express very high levels of foreign proteins in plants. However, TMV vectors are, in general, not efficiently delivered to plant cells by agroinfection. It was determined that agroinfection was very efficient with a 35S promoter-driven TMV replicon that lacked the TMV coat protein gene sequence. This coat protein deletion vector had several useful features as a transient expression system, including improved ease of use, higher protein expression rates, and improved biocontainment. Using this TMV expression vector, some foreign proteins were expressed at levels of 3 to 5 mg/g fresh weight of plant tissue. It is proposed that this new transient expression vector will be a useful tool for expressing recombinant proteins in plants for either research or production purposes.
Large-Scale, Lineage-Specific Expansion of a Bric-a-Brac/Tramtrack/Broad Complex Ubiquitin-Ligase Gene Family in Rice
Authors: Gingerich Derek J. , Hanada Kousuke , Shiu Shin-Han , Vierstra Richard D.
Published: August 2007

Selective ubiquitination of proteins is directed by diverse families of ubiquitin-protein ligases (or E3s) in plants. One important type uses Cullin-3 as a scaffold to assemble multisubunit E3 complexes containing one of a multitude of bric-a-brac/tramtrack/broad complex (BTB) proteins that function as substrate recognition factors. We previously described the 80-member BTB gene superfamily in Arabidopsis thaliana. Here, we describe the complete BTB superfamily in rice (Oryza sativa spp japonica cv Nipponbare) that contains 149 BTB domain–encoding genes and 43 putative pseudogenes. Amino acid sequence comparisons of the rice and Arabidopsis superfamilies revealed a near equal repertoire of putative substrate recognition module types. However, phylogenetic comparisons detected numerous gene duplication and/or loss events since the rice and Arabidopsis BTB lineages split, suggesting possible functional specialization within individual BTB families. In particular, a major expansion and diversification of a subset of BTB proteins containing Meprin and TRAF homology (MATH) substrate recognition sites was evident in rice and other monocots that likely occurred following the monocot/dicot split. The MATH domain of a subset appears to have evolved significantly faster than those in a smaller core subset that predates flowering plants, suggesting that the substrate recognition module in many monocot MATH-BTB E3s are diversifying to ubiquitinate a set of substrates that are themselves rapidly changing. Intriguing possibilities include pathogen proteins attempting to avoid inactivation by the monocot host.
A knowledge‐based engineering tool to estimate cost and weight of composite aerospace structures at the conceptual stage of the design process
Authors: Choi Jin‐Woo , Kelly Don , Raju John
Published: August 2007

Purpose

This paper seeks to address issues related to the development of a knowledge‐based engineering system for estimating manufacturing cost and weight of a composite structure at the conceptual stage of a design.

Design/methodology/approach

The system has been developed in the CATIA V5 knowledge environment and is applied to structures made of composite materials. At the conceptual stage of the design process, a structure is often represented by simple surfaces. The system adds the details necessary to accurately estimate weight and manufacturing cost using geometry and process‐based techniques. Knowledge captured from an expert was used to construct the knowledge base in the system.

Findings

It has been found that the system can provide continuous tracking of the weight and cost as the design evolves. Structural FEA and optimisation using MSC.NASTRAN have been integrated into the design process to enables the designer to conduct “what‐if” analyses to explore different design options involving geometry parameters such as the internal configuration of the structure.

Originality/value

The paper demonstrates that tools embedded in CAD systems can be expected to be able to facilitate the task of estimation of weight and manufacturing cost at the conceptual stage of the design process.