Perceptual Consequences of Early-Onset Hereditary Hearing Loss in the Belgian Waterslager Canary (Serinus Canarius)

Belgian Waterslager canaries (BWS) are bred for a distinctive low-pitched song that includes sounds that are thought to resemble water. This strain of canary has been used in multiple neurobiological and behavioral studies of song learning. These birds have a permanent hereditary hearing loss associated with missing and abnormal hair cells. The hearing deficit develops after hatch, but is present when the birds learn their song. The manner in which these birds process complex sounds indisputably affects the content of their vocalizations; however, no studies have looked at BWS canaries' ability to detect and discriminate sounds other than detection of pure tones in quiet. Thus, the BWS canary provides a unique opportunity to investigate the relationship between the form and function of an auditory system involved in vocal learning. Here I describe a series of psychoacoustic experiments that investigate differences in masking, discrimination, temporal processing, and perception of song elements in BWS canaries and normal-hearing non-BWS canary strains. Spectral and temporal studies of masking showed that frequency resolution and the phase response of the basilar papilla are impaired in BWS canaries. Frequency discrimination was superb at low frequencies, but worse than normal at high frequencies in BWS canaries. Duration and intensity discrimination was not adversely affected by the hearing loss. Temporal resolution was normal or better than normal under some conditions in BWS canaries. Despite the hearing loss, BWS canaries are able to accurately discriminate among strain-specific song syllables as well as syllables of other canary strains. In fact, BWS canaries are actually better than non-BWS canaries at discriminating among BWS canary syllables. These perceptual predispositions in BWS canaries are presumably related to the structural abnormalities of the inner ear, and are likely to play a role in song learning and song maintanence by enhancing the birds' ability to attend to important acoustic features that are characteristic of BWS vocalizations

Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing

An Investigation of Proteolytic, Lipolytic Activity and Biofilm Formation by Psychrotrophic Bacteria Isolated from Buffalo Milk

The aim of this study was to investigate the enzymatic activity of 21 bacteria isolated from refrigerated raw buffalo milk, as well as to evaluate the production of biofilm by these bacteria. Proteolytic, lipolytic and lecithinase activity, as well as the production of exopolysaccharides were evaluated at different temperatures. For all of the psychrotrophic bacteria, biofilm formation on microtiter plates was evaluated at different temperatures and in the presence of residual buffalo and bovine milk. All cultures showed a proteolytic profile while 9 cultures showed lipase activity. Lecithinase production was found in 7 of the evaluated psychrotrophic bacteria. The ability to produce exopolysaccharides was found in 12 bacteria. Of the 21 bacterial isolates, 16 were biofilm producers at 7°C. At 23°C, 20 isolates were found to be biofilm producers. At a temperature of 37°C, biofilm formation by 17 isolates was weak. In the presence of residual buffalo milk, 7 were biofilm producers, while 16 bacteria produced biofilm in residual bovine milk. The results of this study show that many isolates of psychrotrophic bacteria from raw buffalo milk have the potential to produce extracellular enzymes as well as biofilm. This deserves special attention when considering the best practices to recommend during the collection of raw milk in establishments which process milk

The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells

Hair cells of the cochlea are mechanosensors for the perception of sound. Mutations in the LRTOMT gene, which encodes a protein with homology to the catecholamine methyltransferase COMT that is linked to schizophrenia, cause deafness. Here, we show that Tomt/Comt2, the murine ortholog of LRTOMT, has an unexpected function in the regulation of mechanotransduction by hair cells. The role of mTOMT in hair cells is independent of mTOMT methyltransferase function and mCOMT cannot substitute for mTOMT function. Instead, mTOMT binds to putative components of the mechanotransduction channel in hair cells and is essential for the transport of some of these components into the mechanically sensitive stereocilia of hair cells. Our studies thus suggest functional diversification between mCOMT and mTOMT, where mTOMT is critical for the assembly of the mechanotransduction machinery of hair cells. Defects in this process are likely mechanistically linked to deafness caused by mutations in LRTOMT/Tomt

Thermal resistance of proteolytic enzymes produced by psychrotrophic bacteria isolated from buffalo milk

Background and Objective: Psychrotrophic bacteria produce extracellular proteases, resulting in deterioration and reduced shelf life of dairy products. In this study, 21 species of psychotropic bacteria isolated from buffalo milk were selected and the thermal resistance of the proteases produced by these bacteria was evaluated. Materials and Methods: The isolates were tested to evaluate proteolytic activity of buffalo milk agar. The cell-free supernatants from the growing of isolates were obtained for the quantification of enzymatic activity under different pH values (5.5, 7.0 and 8.0). Thermal resistance and the clotting ability of proteolytic enzymes in buffalo and bovine milk substrates were also evaluated. One-way ANOVA test with a critical probability of p1 U mLG1 under at least one of the pH tested. Five isolates produced cell-free supernatants resistant to pasteurization (63.5EC/30 min), following which they were able to coagulate buffalo and bovine milk. The crude enzyme of P. fluorescens PL5.4 showed the greatest enzymatic activity within a wide pH range (4-10) and at an optimum temperature of 40EC. The cell-free supernatant of this isolate resisted to tests with detergents and organic solvents. However, it was not possible to identify the type of protease. Conclusion: The results of this study showed the negative impact of the presence of psychrotrophic bacteria producing proteolytic enzymes in buffalo milk. This is because the enzymes studied caused changes in milk samples, revealing a negative impact on the production of derived products. This is significant, since the buffalo milk produced in Brazil is directed to the production of dairy products

TMIE defines pore and gating properties of the mechanotransduction channel of mammalian cochlear hair cells

TMC1 and TMC2 (TMC1/2) have been proposed to form the pore of the mechanotransduction channel of cochlear hair cells. Here, we show that TMC1/2 cannot form mechanotransduction channels in cochlear hair cells without TMIE. TMIE binds to TMC1/2, and a TMIE mutation that perturbs TMC1/2 binding abolishes mechanotransduction. N-terminal TMIE deletions affect the response of the mechanotransduction channel to mechanical force. Similar to mechanically gated TREK channels, the C-terminal cytoplasmic TMIE domain contains charged amino acids that mediate binding to phospholipids, including PIP2. TMIE point mutations in the C terminus that are linked to deafness disrupt phospholipid binding, sensitize the channel to PIP2 depletion from hair cells, and alter the channel's unitary conductance and ion selectivity. We conclude that TMIE is a subunit of the cochlear mechanotransduction channel and that channel function is regulated by a phospholipid-sensing domain in TMIE with similarity to those in other mechanically gated ion channels

Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats

Naked mole-rats are highly vocal, eusocial, subterranean rodents with, counterintuitively, poor hearing. The causes underlying their altered hearing are unknown. Moreover, whether altered hearing is degenerate or adaptive to their unique lifestyles is controversial. We used various methods to identify the factors contributing to altered hearing in naked and the related Damaraland mole-rats and to examine whether these alterations result from relaxed or adaptive selection. Remarkably, we found that cochlear amplification was absent from both species despite normal prestin function in outer hair cells isolated from naked mole-rats. Instead, loss of cochlear amplification appears to result from abnormal hair bundle morphologies observed in both species. By exploiting a well-curated deafness phenotype-genotype database, we identified amino acid substitutions consistent with abnormal hair bundle morphology and reduced hearing sensitivity. Amino acid substitutions were found in unique groups of six hair bundle link proteins. Molecular evolutionary analyses revealed shifts in selection pressure at both the gene and the codon level for five of these six hair bundle link proteins. Substitutions in three of these proteins are associated exclusively with altered hearing. Altogether, our findings identify the likely mechanism of altered hearing in African mole-rats, making them the only identified mammals naturally lacking cochlear amplification. Moreover, our findings suggest that altered hearing in African mole-rats is adaptive, perhaps tailoring hearing to eusocial and subterranean lifestyles. Finally, our work reveals multiple, unique evolutionary trajectories in African mole-rat hearing and establishes species members as naturally occurring disease models to investigate human hearing loss

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats

Naked mole-rats are highly vocal, eusocial, subterranean rodents with, counterintuitively, poor hearing. The causes underlying their altered hearing are unknown. Moreover, whether altered hearing is degenerate or adaptive to their unique lifestyles is controversial. We used various methods to identify the factors contributing to altered hearing in naked and the related Damaraland mole-rats and to examine whether these alterations result from relaxed or adaptive selection. Remarkably, we found that cochlear amplification was absent from both species despite normal prestin function in outer hair cells isolated from naked mole-rats. Instead, loss of cochlear amplification appears to result from abnormal hair bundle morphologies observed in both species. By exploiting a well-curated deafness phenotype-genotype database, we identified amino acid substitutions consistent with abnormal hair bundle morphology and reduced hearing sensitivity. Amino acid substitutions were found in unique groups of six hair bundle link proteins. Molecular evolutionary analyses revealed shifts in selection pressure at both the gene and the codon level for five of these six hair bundle link proteins. Substitutions in three of these proteins are associated exclusively with altered hearing. Altogether, our findings identify the likely mechanism of altered hearing in African mole-rats, making them the only identified mammals naturally lacking cochlear amplification. Moreover, our findings suggest that altered hearing in African mole-rats is adaptive, perhaps tailoring hearing to eusocial and subterranean lifestyles. Finally, our work reveals multiple, unique evolutionary trajectories in African mole-rat hearing and establishes species members as naturally occurring disease models to investigate human hearing loss.</p