Growth Hormone Promotes Hair Cell Regeneration in the Zebrafish (Danio rerio) Inner Ear following Acoustic Trauma

BACKGROUND: Previous microarray analysis showed that growth hormone (GH) was significantly upregulated following acoustic trauma in the zebrafish (Danio rerio) ear suggesting that GH may play an important role in the process of auditory hair cell regeneration. Our objective was to examine the effects of exogenous and endogenous GH on zebrafish inner ear epithelia following acoustic trauma. METHODOLOGY/PRINCIPAL FINDINGS: We induced auditory hair cell damage by exposing zebrafish to acoustic overstimulation. Fish were then injected intraperitoneally with either carp GH or buffer, and placed in a recovery tank for either one or two days. Phalloidin-, bromodeoxyuridine (BrdU)-, and TUNEL-labeling were used to examine hair cell densities, cell proliferation, and apoptosis, respectively. Two days post-trauma, saccular hair cell densities in GH-treated fish were similar to that of baseline controls, whereas buffer-injected fish showed significantly reduced densities of hair cell bundles. Cell proliferation was greater and apoptosis reduced in the saccules, lagenae, and utricles of GH-treated fish one day following trauma compared to controls. Fluorescent in situ hybridization (FISH) was used to examine the localization of GH mRNA in the zebrafish ear. At one day post-trauma, GH mRNA expression appeared to be localized perinuclearly around erythrocytes in the blood vessels of the inner ear epithelia. In order to examine the effects of endogenous GH on the process of cell proliferation in the ear, a GH antagonist was injected into zebrafish immediately following acoustic trauma, resulting in significantly decreased cell proliferation one day post-trauma in all three zebrafish inner ear end organs. CONCLUSIONS/SIGNIFICANCE: Our results show that exogenous GH promotes post-trauma auditory hair cell regeneration in the zebrafish ear through stimulating proliferation and suppressing apoptosis, and that endogenous GH signals are present in the zebrafish ear during the process of auditory hair cell regeneration

Somatic ‘Soluble’ Adenylyl Cyclase Isoforms Are Unaffected in Sacytm1Lex/Sacytm1Lex ‘Knockout’ Mice

BACKGROUND: Mammalian Soluble adenylyl cyclase (sAC, Adcy10, or Sacy) represents a source of the second messenger cAMP distinct from the widely studied, G protein-regulated transmembrane adenylyl cyclases. Genetic deletion of the second through fourth coding exons in Sacy(tm1Lex)/Sacy(tm1Lex) knockout mice results in a male sterile phenotype. The absence of any major somatic phenotype is inconsistent with the variety of somatic functions identified for sAC using pharmacological inhibitors and RNA interference. PRINCIPAL FINDINGS: We now use immunological and molecular biological methods to demonstrate that somatic tissues express a previously unknown isoform of sAC, which utilizes a unique start site, and which 'escapes' the design of the Sacy(tm1Lex) knockout allele. CONCLUSIONS/SIGNIFICANCE: These studies reveal increased complexity at the sAC locus, and they suggest that the known isoforms of sAC play a unique function in male germ cells

Conservation of energy-momentum of matter as the basis for the gauge theory of gravitation

According to Yang \& Mills (1954), a {\it conserved} current and a related rigid (`global') symmetry lie at the foundations of gauge theory. When the rigid symmetry is extended to a {\it local} one, a so-called gauge symmetry, a new interaction emerges as gauge potential $A$; its field strength is $F\sim {\rm curl} A$. In gravity, the conservation of the energy-momentum current of matter and the rigid translation symmetry in the Minkowski space of special relativity lie at the foundations of a gravitational gauge theory. If the translation invariance is made local, a gravitational potential $\vartheta$ arises together with its field strength $T\sim {\rm curl}\,\vartheta$. Thereby the Minkowski space deforms into a Weitzenb\"ock space with nonvanishing torsion $T$ but vanishing curvature. The corresponding theory is reviewed and its equivalence to general relativity pointed out. Since translations form a subgroup of the Poincar\'e group, the group of motion of special relativity, one ought to straightforwardly extend the gauging of the translations to the gauging of full Poincar\'e group thereby also including the conservation law of the {\it angular momentum} current. The emerging Poincar\'e gauge (theory of) gravity, starting from the viable Einstein-Cartan theory of 1961, will be shortly reviewed and its prospects for further developments assessed.Comment: 46 pages, 4 figures, minor corrections, references added, contribution to "One Hundred Years of Gauge Theory" edited by S. De Bianchi and C. Kiefe