Feedback regulation and the intracellular protein profile of Streptomyces griseus in a cycloheximide fermentation

Two-dimensional gel electrophoresis (2-D PAGE) was used to study the intracellular protein profile of Streptomyces griseus in relation to cycloheximide (CH) biosynthesis. Four proteins (CR1-CR4) were found to be significantly and specifically repressed by addition of the antibiotic (1 g/l at 72 h) to a producing fermentation. Synthesis of these proteins was specific to the idiophase, concurrent with CH production. Initial addition of CH to the production medium resulted in slightly lower synthesis rates of two of the proteins (CR1 and CR2), while significantly delaying the onset of synthesis of the other two (CR3 and C4). Finally, neutral polymetric resin was added to the fermentation to alleviate feedback regulation of CH synthesis, giving roughly a twofold increase in the antibiotic production rate. Production of proteins CR3 and CR4 was increased approximately tenfold immediately following resin addition, but returned to the control rate of synthesis after 24 h.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46761/1/253_2004_Article_BF00166779.pd

Losartan Decreases p42/44 MAPK Signaling and Preserves LZ+ MYPT1 Expression

Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure

Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E(2 )from human articular chondrocytes

BACKGROUND: Sphingosine-1-phosphate (S1P), a downstream metabolite of ceramide, induces various bioactivities via two distinct pathways: as an intracellular second messenger or through receptor activation. The receptor for S1P (S1PR) is the family of Endothelial differentiation, sphingolipid G-protein-coupled receptor (EDG). We have here attempted to reveal the expression of EDG/S1PR in human articular chondrocytes (HAC), exploring the implications of S1P in cartilage degradation. METHODS: Articular cartilage specimens were obtained from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or traumatic fracture (representing normal chondrocytes) who underwent joint surgery. Isolated HAC were cultured in vitro by monolayer and stimulated with S1P in the presence or absence of inhibitors of signaling molecules. Stimulated cells and culture supernatants were collected and subjected to analyses using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). RESULTS: All of the tested HAC samples showed positive results in terms of EDG/S1PR expression in basal condition. When HAC was stimulated with S1P, a significant increase in prostaglandin (PG) E(2 )production was observed together with enhanced expression of cyclooxygenase (COX)-2. S1P stimulated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in HAC, and the PGE(2 )induction was abrogated by PD98059 and SB203580. Pertussis toxin inhibited the PGE(2 )induction from HAC by S1P, suggesting an essential role for Gi protein. S1P also attenuated the expression of proteoglycan aggrecan, a component of cartilage matrix, in HAC at transcriptional level. CONCLUSION: It was suggested that the S1P-induced PGE(2 )was at least in part involved in the aggrecan-suppressing effect of S1P, seeing as COX inhibitors attenuated the effect. Accordingly, S1P might play an important role in cartilage degradation in arthritides

Self Assessment in Insects: Honeybee Queens Know Their Own Strength

Contests mediate access to reproductive opportunities in almost all species of animals. An important aspect of the evolution of contests is the reduction of the costs incurred during intra-specific encounters to a minimum. However, escalated fights are commonly lethal in some species like the honeybee, Apis mellifera. By experimentally reducing honeybee queens' fighting abilities, we demonstrate that they refrain from engaging in lethal contests that typically characterize their reproductive dominance behavior and coexist peacefully within a colony. This suggests that weak queens exploit an alternative reproductive strategy and provides an explanation for rare occurrences of queen cohabitation in nature. Our results further indicate that self-assessment, but not mutual assessment of fighting ability occurs prior to and during the agonistic encounters

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Development and preliminary validation of Brace Questionnaire (BrQ): a new instrument for measuring quality of life of brace treated scoliotics

BACKGROUND: The quality of life among children with idiopathic scoliosis during their adolescence has been reported to be affected by the brace itself. However, a controversy exists whether brace treated scoliotics experience a poor quality of life, thus there is a need for the development of a brace-oriented instrument, as the now-existing questionnaires that are commonly used, such as the SRS -22, take into consideration the effects of both the conservative and the surgical treatment on quality of life of scoliotic children. The aim of the present study is to assess the validity and reliability of Brace Questionnaire (BrQ), a new instrument for measuring quality of life of scoliotic adolescents who are treated conservatively with a brace. MATERIAL-METHOD: Methodology of development involved literature review, patient and health care professionals' in-depth interviews and content validity analysis on patients. A validation study was performed on 28 brace treated scoliotic children aged between 9 and 18 years old. BrQ was assessed for the following psychometric properties: item convergent validity, floor and ceiling effects, internal consistency reliability, clinical validity and responsiveness to change. RESULTS: BrQ is self administrated and developmentally appropriate for ages 9 to 18 years old and is consisted of 34 Likert-scale items associated with eight domains: general health perception, physical functioning, emotional functioning, self esteem and aesthetics, vitality, school activity, bodily pain and social functioning of scoliotic children treated conservatively with a brace. The subscales of these eight dimensions can be combined to produce a total score. Higher scores mean a better quality of life. An item convergent validity ≥ 0.40 was satisfied by all items in the present study. A satisfactory internal consistency reliability for the BrQ was recorded (Cronbach's alpha coefficient was 0.82). There were no floor or ceiling effects. The correlation between BrQ overall scores and mild and moderate scoliosis was statistically significant (p < 0.001), revealing high clinical validity. An increase in effect sizes for the patient with improved scoliotic curves indicates that the BrQ is responsive to change in health status. CONCLUSION: BrQ is reliable, valid and responsive to change in adolescents with IS who are treated conservatively with a brace

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg