Effects of simultaneous exercise and loud music on hearing acuity and auditory function

Hearing acuity can be reduced temporarily after exposure to loud noise, and the physiological responses that occur with exercise may enhance this effect. Currently, it is not known whether short-term reductions in hearing acuity after noise exposure and exercise are a result of temporary changes in auditory function. Therefore, the purpose of this investigation was to determine the acute effects of simultaneous exercise and loud music on hearing acuity and auditory function in young, healthy women. Nine women (age = 22 +/- 5 years, body mass index = 23.9 +/- 2.2, Vo(2)peak = 30.6 +/- 6.0 ml x kg(-1) x min(-1)) with normal hearing thresholds (<20 dB hearing level) underwent each of 3 conditions in a randomized counterbalanced design: (a) loud music exposure of 90 to 95 dB sound pressure level for 20 minutes, (b) exercise at 60% Vo(2)peak on a cycle ergometer for 20 minutes, and (c) simultaneous exercise and music exposure for 20 minutes. Hearing acuity and auditory function were assessed via pure-tone hearing thresholds and distortion product otoacoustic emission amplitudes, respectively, at frequencies of 2, 3, 4, 6, and 8 kHz presented in random order before and after each condition. Results indicate that hearing acuity and auditory function remained unaltered after exposure to each condition (p > 0.05). These findings provide evidence that hearing acuity and auditory function in young women do not change after short-term exposure to moderate-intensity exercise and loud music. Thus, listening to loud music with earphones during moderate-intensity exercise does not pose acute hearing health concerns for young physically fit adults with normal hearing.     

Apoptosis in yeasts

Although yeasts lack some elements of the complex apoptotic machinery of metazoan cells, recent studies show that many features of apoptosis, including a caspase-like activity, can be induced in these organisms by DNA damage and other apoptotic triggers. These remarkable findings provide a compelling argument for increased efforts to bring the powerful genetic approaches available to yeast researchers more directly to bear on questions related to apoptosis and its induction or inhibition by drugs. Yeasts may provide a particularly useful model for understanding connections between DNA damage, cell cycle regulation and apoptosis. Here we summarize these recent findings and explore their implications, particularly for the development of more effective therapeutic strategies for treating cancer.     

Mathematical models of cochlear nucleus onset neurons: I. Point neuron with many weak synaptic inputs

The cochlear nucleus (CN) presents a unique opportunity for quantitatively studying input-output transformations by neurons because it gives rise to a variety of different response types from a relatively homogeneous input source, the auditory nerve (AN). Particularly interesting among CN neurons are Onset (On) neurons, which have a prominent response to the onset of sustained sounds followed by little or no response in the steady-state. On neurons contrast sharply with their AN inputs, which respond vigorously throughout stimuli. On neurons can entrain to stimuli (firing once per cycle of a periodic stimulus) at up to 1000 Hz, unlike their AN inputs. To understand the mechanisms underlying these response patterns, we tested whether an integrate-to-threshold point-neuron model with a fixed refractory period can account for On discharge patterns for tones, systematically examining the effect of membrane time constant and the number and strength of the exclusively excitatory AN synaptic inputs. To produce both onset responses to high-frequency tone bursts and entrainment to a broad range of low-frequency tones, the model must have a short time constant (0.125 ms) and a large number (>100) of weak synaptic inputs, properties that are consistent with the electrical properties and anatomy of On-responding cells. With these parameters, the model acts like a coincidence detector with a threshold-like relationship between the instantaneous discharge rates of the output and the inputs. Onset responses to high-frequency tone bursts result because the threshold effect enhances the initial response of the AN inputs and suppresses their relatively lower sustained response. However, when the model entrains across a broad range of frequencies, it also produces short interspike intervals at the onset of high-frequency tone bursts, a response pattern not found in all types of On neurons. These results show a tradeoff, that may be a general property of many neurons, between following rapid stimulus fluctuations and responding without short interspike intervals at the onset of sustained stimuli.     

Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis

Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity mapping of deletions (HOMOD) analysis. This method of analysis involved the use of highly polymorphic microsatellite markers and statistics to identify regions of hemizygous deletion in unmatched melanoma cell line DNAs. Regions of loss were defined by the presence of an extended region of homozygosity (ERH) at > or =5 adjacent markers and having a statistical probability of < or =.001. Significant ERHs were similar in nature to deletions identified by LOH analyses performed on uncultured melanomas, although a higher frequency of loss (24 [60%] of 40 vs. 16 [34%] of 47) was observed in the cell lines. Overall, six small regions of overlapping deletions (SROs) were identified on chromosome 11 flanked by the markers D11S1338/D11S907 (11p13-15.5 [SRO1]), D11S1344/D11S11385 (11p11.2 [SRO2]), D11S917/D11S1886 (11q21-22.3 [SRO3]), D11S927/D11S4094 (11q23 [SRO4]), AFM210ve3/D11S990 (11q24 [SRO5]), and D11S1351/D11S4123 (11q24-25 [SRO6]). We propose that HOMOD analysis can be used as an adjunct to LOH analysis in the localization of tumor-suppressor genes.     

Phosphorylation of serine 51 in initiation factor 2 alpha (eIF2 alpha) promotes complex formation between eIF2 alpha(P) and eIF2B and causes inhibition in the guanine nucleotide exchange activity of eIF2B

Phosphorylation of serine 51 residue on the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha) inhibits the guanine nucleotide exchange (GNE) activity of eIF2B, presumably, by forming a tight complex with eIF2B. Inhibition of the GNE activity of eIF2B leads to impairment in eIF2 recycling and protein synthesis. We have partially purified the wild-type (wt) and mutants of eIF2alpha in which the serine 51 residue was replaced with alanine (51A mutant) or aspartic acid (51D mutant) in the baculovirus system. Analysis of these mutants has provided novel insight into the role of 51 serine in the interaction between eIF2 and eIF2B. Neither mutant was phosphorylated in vitro. Both mutants decreased eIF2alpha phosphorylation occurring in hemin and poly(IC)-treated reticulocyte lysates due to the activation of double-stranded RNA-dependent protein kinase (PKR). However, addition of 51D, but not 51A mutant eIF2alpha protein promoted inhibition of the GNE activity of eIF2B in hemin-supplemented rabbit reticulocyte lysates in which relatively little or no endogenous eIF2alpha phosphorylation occurred. The 51D mutant enhanced the inhibition in GNE activity of eIF2B that occurred in hemin and poly(IC)-treated reticulocyte lysates where PKR is active. Our results show that the increased interaction between eIF2 and eIF2B protein, occurring in reticulocyte lysates due to increased eIF2alpha phosphorylation, is decreased significantly by the addition of mutant 51A protein but not 51D. Consistent with the idea that mutant 51D protein behaves like a phosphorylated eIF2alpha, addition of this partially purified recombinant subunit, but not 51A or wt eIF2alpha, increases the interaction between eIF2 and 2B proteins in actively translating hemin-supplemented lysates. These findings support the idea that phosphorylation of the serine 51 residue in eIF2alpha promotes complex formation between eIF2alpha(P) and eIF2B and thereby inhibits the GNE activity of eIF2B.     

Chemosensory proteins from the proboscis of mamestra brassicae

Soluble, low molecular weight proteins were immunodetected in proboscis extracts of Mamestra brassicae males by Western blot, using antibodies raised against the general odorant-binding protein of the moth Antheraea polyphemus. The same antibodies weakly labelled the sensillum lymph and subcuticular space of sensilla styloconica on ultrathin sections of the proboscis. The morphology of sensilla styloconica is described. The immunodetected proteins yielded several N-terminal sequences, three of which showed strong affinity for tritiated analogues of pheromonal compounds of M. brassicae in binding assays. The cDNAs coding for these sequences were cloned and it was shown that the new proteins are related to the OS-D protein of DROSOPHILA: They are named chemosensory proteins (CSP-MBRA:A1-CSP-MBRA:A5 and CSP-MBRA:B1 and CSP-MBRA:B2) and may have an odorant-binding protein-like function. A common localization in both olfaction and taste organs suggests a physiological role depending on the cellular environment.     

Profilin plays a role in cell elongation, cell shape maintenance, and flowering in Arabidopsis

Profilin (PFN) is an ubiquitous, low-M(r), actin-binding protein involved in the organization of the cytoskeleton of eukaryotes including higher plants. PFNs are encoded by a multigene family in Arabidopsis. We have analyzed in vivo functions of Arabidopsis PFN by generating transgenic plants carrying a 35S-PFN-1 or 35S-antisense PFN-1 transgene. Etiolated seedlings underexpressing PFN (PFN-U) displayed an overall dwarf phenotype with short hypocotyls whose lengths were 20% to 25% that of wild type (WT) at low temperatures. Light-grown PFN-U plants were smaller in stature and flowered early. Compared with equivalent cells in WT, most cells in PFN-U hypocotyls and roots were shorter, but more isodiametric, and microscopic observations of etiolated PFN-U hypocotyls revealed a rough epidermal surface. In contrast, light-grown seedlings overexpressing PFN had longer roots and root hair although etiolated seedlings overexpressing PFN were either the same size or slightly longer than WT seedlings. Transgenic seedlings harboring a PFN-1-GUS transgene directed expression in root and root hair and in a ring of cells at the elongating zone of the root tip. As the seedlings matured PFN-1-GUS was mainly expressed in the vascular bundles of cotyledons and leaves. Our results show that Arabidopsis PFNs play a role in cell elongation, cell shape maintenance, polarized growth of root hair, and unexpectedly, in determination of flowering time.     

Greenhouse and field evaluations of transgenic canola against diamondback moth, shape Plutella xylostella, and corn earworm, shape Helicoverpa zea

Canola (Brassica napus L.) cultivars Oscar and Westar, engineered with a Bacillus thuringiensis (Bt) cryIA(c) gene, were evaluated for resistance to lepidopterous pests, diamondback moth, Plutella xylostella L. (Plutellidae) and corn earworm, Helicoverpa zea (Boddie) (Noctuidae) in greenhouse and field conditions. In greenhouse preference assays conducted at vegetative and flowering plant stages, transgenic plants recorded very low levels of damage. A 100% diamondback moth mortality and 90% corn earworm mortality were obtained on transgenic plants in greenhouse antibiosis assays. The surviving corn earworm larvae on transgenic plants had reduced head capsule width and body weight. Mortality of diamondback moth and corn earworm were 100% and 95%, respectively, at different growth stages (seedling, vegetative, bolting, and flowering) on the transgenic plants in greenhouse tests. In field tests conducted during 1995–1997, plots were artificially infested with neonates of diamondback moth or corn earworm or left for natural infestation. Transgenic plants in all the treatments were highly resistant to diamondback moth and corn earworm larvae and had very low levels of defoliation. Plots infested with diamondback moth larvae had greater damage in both seasons as compared with corn earworm infested plots and plots under natural infestation. After exposure to defoliators, transgenic plants usually had higher final plant stand and produced more pods and seeds than non-transgenic plants. Diamondback moth injury caused the most pronounced difference in plant stand and pod and seed number between transgenic and non-transgenic plants. Our results suggest that transgenic canola could be used for effective management of diamondback moth and corn earworm on canola.     

Use of microarray analysis to study gene expression in the avian epiphyseal growth plate

Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. RT-PCR was used to confirm the identity of a select number of genes. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability. Transferrin was the most highly up-regulated (321-fold) gene associated with chondrocyte hypertrophy. Immunohistochemistry localized this peptide adjacent to the penetrating blood vessels in the growth plate of 3-week-old chicks. Fibulin, OC-116, DMP-1 and PHEX were among the expanded number of genes associated with extracellular matrix metabolism. The presence of NELL2, ATOH8 and PLEXIN suggests a neuronal involvement in growth plate physiology. In addition, the expression of a large number of genes associated with angiogenesis and cellular stress was up-regulated. These processes are important to the physiology and survival of chondrocytes in the unique and stressful environment of the epiphyseal growth plate.