2,434 research outputs found
Inhibition of 5-lipoxygenase downregulates stemness and kills prostate cancer stem cells by triggering apoptosis via activation of c-Jun N-terminal kinase.
The cancer stem cell (CSC) concept suggests that neoplastic clones are maintained exclusively by a rare group of cells possessed with stem cell properties. CSCs are characterized by features that include self-renewal, pluripotency and tumorigenicity, and are thought to be solely responsible for tumor recurrence and metastasis. A hierarchically organized CSC model is becoming increasingly evident for various types of cancer, including prostate cancer. The CD44 (+), CD133 (+) cell subpopulations were isolated from human prostate tumors which exhibit stem-like properties showing therapeutic-resistance, capacity of self-renewal, and exact recapitulation of the original tumor in vivo. Thus, an important challenge is to find measures to eliminate these cancer stem cells, which will stop tumor growth and prevent disease-recurrence. However, knowledge about molecular features critical for the survival of prostate cancer stem cells (PCSC) is meager. Here we report that inhibition of 5-lipoxygenase (5-Lox) by shRNA or MK591 dramatically kills PCSC by inducing apoptosis, suggesting that 5-Lox plays an essential role in the survival of PCSC. Interestingly, MK591 treatment decreases protein levels and inhibits transcriptional activities of Nanog and c-Myc. Since Nanog and c-Myc play important roles as stemness factors, our findings indicate that the 5-Lox activity plays a causal role in maintaining prostate cancer stemness via regulation of Nanog and c-Myc, and suggest that further exploration of 5-Lox-mediated signaling in PCSC may lead to development of novel, target-based, durable strategies to effectively block development and growth of prostate tumors, and prevent prostate cancer recurrence
Asymptomatic retained gauge piece (gossypiboma) for 10 years after posterior spinal surgery - A case report
A young old male presented with a 2 months history of recurrent disc prolapse 10 years after prior surgery. He was operated for L4-L5 disc prolapse 10 years ago. Fresh MRI showed prolapsed intervertebral disk (PIVD) at L5-S1 level with a spherical mass lesion of 2.5x2x2 cm with well defined margin in the left paraspinal area adjacent to L5 lamina. The patient had symptoms of L5-S1 PIVD but absolutely no local or systemic symptom for the mass. On exploration, a retained gauge piece was found in the left paraspinal area
Erratum: Antiplatelet effects of dietary nitrate in healthy volunteers: Involvement of cGMP and influence of sex (Free Radical Biology and Medicine (2013) 65 (1521-1532))
A correction to an error in the original published fi
Color & Weak triplet scalars, the dimuon asymmetry in decay, the top forward-backward asymmetry, and the CDF dijet excess
The new physics required to explain the anomalies recently reported by the D0
and CDF collaborations, namely the top forward-backward asymmetry (FBA), the
like-sign dimuon charge asymmetry in semileptonic b decay, and the CDF dijet
excess, has to feature an amount of flavor symmetry in order to satisfy the
severe constrains arising from flavor violation. In this paper we show that,
once baryon number conservation is imposed, color & weak triplet scalars with
hypercharge can feature the required flavor structure as a consequence
of standard model gauge invariance. The color & weak triplet model can
simultaneously explain the top FBA and the dimuon charge asymmetry or the
dimuon charge asymmetry and the CDF dijet excess. However, the CDF dijet excess
appears to be incompatible with the top FBA in the minimal framework. Our model
for the dimuon asymmetry predicts the observed pattern in the
region of parameter space required to explain the top FBA, whereas our model
for the CDF dijet anomaly is characterized by the absence of beyond the SM
b-quark jets in the excess region. Compatibility of the color & weak triplet
with the electroweak constraints is also discussed. We show that a Higgs boson
mass exceeding the LEP bound is typically favored in this scenario, and that
both Higgs production and decay can be significantly altered by the triplet.
The most promising collider signature is found if the splitting among the
components of the triplet is of weak scale magnitude.Comment: references added, published versio
A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene
BACKGROUND: Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates. METHODS: In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major. RESULTS: A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages. CONCLUSION: The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites
Working Group Report: Heavy-Ion Physics and Quark-Gluon Plasma
This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09
which was part of Working Group-4. Discussion and work on some aspects of
Quark-Gluon Plasma believed to have created in heavy-ion collisions and in
early universe are reported.Comment: 20 pages, 6 eps figures, Heavy-ion physics and QGP activity report in
"IX Workshop on High Energy Physics Phenomenology (WHEPP-09)" held in
Institute of Physics, Bhubaneswar, India, during January 3-14, 2006. To be
published in PRAMANA - Journal of Physics (Indian Academy of Science
Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK
\ua9 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) \ub5mol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) \ub5mol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 \ub5mol/L triggering urgent referral, and those >2.0 and <5.0 \ub5mol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder
Radiative contribution to neutrino masses and mixing in SSM
In an extension of the minimal supersymmetric standard model (popularly known
as the SSM), three right handed neutrino superfields are introduced to
solve the -problem and to accommodate the non-vanishing neutrino masses
and mixing. Neutrino masses at the tree level are generated through parity
violation and seesaw mechanism. We have analyzed the full effect of one-loop
contributions to the neutrino mass matrix. We show that the current three
flavour global neutrino data can be accommodated in the SSM, for both
the tree level and one-loop corrected analyses. We find that it is relatively
easier to accommodate the normal hierarchical mass pattern compared to the
inverted hierarchical or quasi-degenerate case, when one-loop corrections are
included.Comment: 51 pages, 14 figures (58 .eps files), expanded introduction, other
minor changes, references adde
The Universal One-Loop Effective Action
We present the universal one-loop effective action for all operators of
dimension up to six obtained by integrating out massive, non-degenerate
multiplets. Our general expression may be applied to loops of heavy fermions or
bosons, and has been checked against partial results available in the
literature. The broad applicability of this approach simplifies one-loop
matching from an ultraviolet model to a lower-energy effective field theory
(EFT), a procedure which is now reduced to the evaluation of a combination of
matrices in our universal expression, without any loop integrals to evaluate.
We illustrate the relationship of our results to the Standard Model (SM) EFT,
using as an example the supersymmetric stop and sbottom squark Lagrangian and
extracting from our universal expression the Wilson coefficients of
dimension-six operators composed of SM fields.Comment: 30 pages, v2 contains additional comments and corrects typos, version
accepted for publication in JHE
In-Vitro Helix Opening of M. tuberculosis oriC by DnaA Occurs at Precise Location and Is Inhibited by IciA Like Protein
BACKGROUND: Mycobacterium tuberculosis (M.tb), the pathogen that causes tuberculosis, is capable of staying asymptomatically in a latent form, persisting for years in very low replicating state, before getting reactivated to cause active infection. It is therefore important to study M.tb chromosome replication, specifically its initiation and regulation. While the region between dnaA and dnaN gene is capable of autonomous replication, little is known about the interaction between DnaA initiator protein, oriC origin of replication sequences and their negative effectors of replication. METHODOLOGY/PRINCIPAL FINDINGS: By KMnO(4) mapping assays the sequences involved in open complex formation within oriC, mediated by M.tb DnaA protein, were mapped to position -500 to -518 with respect to the dnaN gene. Contrary to E. coli, the M.tb DnaA in the presence of non-hydrolysable analogue of ATP (ATPgammaS) was unable to participate in helix opening thereby pointing to the importance of ATP hydrolysis. Interestingly, ATPase activity in the presence of supercoiled template was higher than that observed for DnaA box alone. M.tb rRv1985c, a homologue of E.coli IciA (Inhibitor of chromosomal initiation) protein, could inhibit DnaA-mediated in-vitro helix opening by specifically binding to A+T rich region of oriC, provided the open complex formation had not initiated. rIciA could also inhibit in-vitro replication of plasmid carrying the M.tb origin of replication. CONCLUSIONS/SIGNIFICANCE: These results have a bearing on the functional role of the important regulator of M.tb chromosomal replication belonging to the LysR family of bacterial regulatory proteins in the context of latency
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