Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.

Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon’s bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage

Cellulite and extracorporeal Shockwave therapy (CelluShock-2009) - a Randomized Trial

<p>Abstract</p> <p>Background</p> <p>Cellulite is a widespread problem involving females' buttocks and thighs based on the female specific anatomy. Given the higher number of fat cells stored in female fatty tissue in contrast to males, and the aging process of connective tissue leads to an imbalance between lipogenesis and lipolysis with subsequent large fat cells bulging the skin. In addition, microcirculatory changes have been suggested, however remain largely unknown in a controlled clinical setting. We hypothesize that the combination of extracorporeal shockwave and a daily gluteal muscle strength program is superior to the gluteal muscle strength program alone in cellulite.</p> <p>Methods/Design</p> <p>Study design: Randomized-controlled trial. IRB approval was granted at Hannover Medical School, Germany on May 22, 2009. For allocation of participants, a 1:1 ratio randomization was performed using opaque envelopes for the concealment of allocation. Reporting: according to CONSORT 2010. Eligible patients were females aged 18 or over and 65 or younger with cellulite with documented cellulite 1°-4° according to the Nürnberger score. Exclusion criteria were suspected or evident pregnancy, no cellulite, no informed consent or age under 18 years or above 65 years. Patients were recruited by advertisements in local regional newspapers and via the Internet. Analysis: Intention-to-treat. Outcome parameters: a) Photonumeric severity scale, b) Nürnberger Score, c) circumference measurements, d) capillary blood flow, e) tissue oxygen saturation, f) postcapillary venous blood flow. Intervention group: Six sessions of extracorporeal focused shock wave for six sessions (2000 impulses, 0,25 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Control group: Six sessions of sham extracorporeal focused shock wave for six sessions (2000 impulses, 0,01 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Follow-up: 12 weeks. Blinding was achieved for all participants enrolled in the trial, the photograph taking the digital images for the primary outcome measure, the two assessors of the outcome measures, all additional health care providers and for the analyst from the biometrical department. Only one researcher (BJ) was aware of the group assignment performing the randomisation and the extracorporeal shock wave therapy.</p> <p>Discussion</p> <p>This randomised-controlled trial will provide much needed evidence on the clinical effectiveness of focused extracorporal shock wave therapy as an adjunct to gluteal strength training in females suffering cellulite.</p> <p>ClinicalTrials.gov identifier</p> <p>NCT00947414</p

Measurement of reproductive performance in Tü wild-type fish, F₁ generation.

Reproductive performance for the F1 (A, B) AB wild-type strain and (C, D) Tü wild-type strain. (A) Fecundity defined as the total number of live embryos spawned and (B) viability defined as the percentage of live embryos at 24-hours post fertilization. Data shown as the mean ± standard deviation. No significant differences were measured in either fecundity or viability, n = 3 represented by 30 fish from each growth treatment.</p

Growth curves of two F₀ wild-type strains from 5 to 60 DPF.

Mean total body length for two F0 generation wild-type strains, (A) AB and (B) Tü. Growth curves are represented by mean ± standard deviation. Open circles = LF, closed squares = HF.</p

Initial reproductive performance of fish from LF and HF.

Values recorded at first successful group spawn of 35 fish. Fish were allowed to spawn for a total of 30 minutes.</p

Growth Curves of two F₁ wild-type lines from 5 to 90 DPF.

Growth curves for two F1 generation wildtype lines (offspring of F0), (A) AB and (B) Tü from 5 to 90 DPF. Slow growth curves are represented by mean ± standard deviation. Open circles = LF from F0 LF parents, closed squares = LF from F0 HF parents.</p

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Post spawn total fish weight (mg).

Total fish weight after each spawning trial is represented by • for fish in the HF group and □ for fish in the LF group. A = AB–F0, B = Tü–F0, C = AB–F1 and D = Tü–F1. No significant differences are reported in weight over the 8 weeks fish were spawned. (TIF)</p

Rotifer & <i>Artemia</i> delivery per tank per day.

(A) Daily rotifer concentration delivered per growth treatment, excluding weekends (day 8 & 9). Open circles = LF, closed squares = HF. (B) Daily Artemia nauplii delivered per growth treatment, excluding weekends. Open circles = LF, closed squares = HF.</p