Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling

Myosin-1c (also known as myosin-Ibeta) has been proposed to mediate the slow component of adaptation by hair cells, the sensory cells of the inner ear. To test this hypothesis, we mutated tyrosine-61 of myosin-1c to glycine, conferring susceptibility to inhibition by N(6)-modified ADP analogs. We expressed the mutant myosin-1c in utricular hair cells of transgenic mice, delivered an ADP analog through a whole-cell recording pipette, and found that the analog rapidly blocked adaptation to positive and negative deflections in transgenic cells but not in wild-type cells. The speed and specificity of inhibition suggests that myosin-1c participates in adaptation in hair cells.     

Validation of an electronic jump mat to assess stretch-shortening cycle function

The purpose of this investigation was to determine the concurrent validity of a commonly used electronic switch mat (ESM), or jump mat, compared with force plate (FP) data. The efficiency of collection and accuracy of data are paramount to athlete and player field testing for the strength and conditioning coach who often has access only to a jump mat. Ten subjects from 5 different sporting backgrounds completed 3 squat jumps (SJs), 3 countermovement jumps (CMJs), and 3 drop jumps (DJs). The jumps were performed on an AMTI FP operating at 1,000 Hz with an ESM positioned on top of the platform. All the subjects were experienced with the protocols involved with jump testing. The resulting absolute errors between FP and ESM data were 0.01, 0.02, and 0.01 m for CMJ, SJ, and DJ heights, respectively. However, the coefficient of variation for the DJ contact time (CT) was 57.25%, CMJ (r = 0.996), and SJ (r = 0.958) heights correlated very strongly with force platform data, and DJ data were not as strong (r = 0.683). Confidence interval tests revealed bias toward CMJ and SJ (p < 0.05). The jump mat can accurately calculate the CMJ height, SJ height, and reactive strength index for all the 3 jump protocols. However, the faster CTs and rapid movements involved in a DJ may limit its reliability when giving measures of CT, flight time, and height jumped for DJs. Strength and conditioning coaches can use such a jump mat device with the confidence that it is accurately producing valid measurements of their athlete's performance for CMJ and SJ slow SSC protocols.     

Distribution Dynamics of Recombinant Lactobacillus in the Gastrointestinal Tract of Neonatal Rats

One approach to deliver therapeutic agents, especially proteins, to the gastro-intestinal (GI) tract is to use commensal bacteria as a carrier. Genus Lactobacillus is an attractive candidate for use in this approach. However, a system for expressing exogenous proteins at a high level has been lacking in Lactobacillus. Moreover, it will be necessary to introduce the recombinant Lactobacillus into the GI tract, ideally by oral administration. Whether orally administered Lactobacillus can reach and reside in the GI tract has not been explored in neonates. In this study, we have examined these issues in neonatal rats. To achieve a high level of protein expression in Lactobacillus, we tested the impact of three promoters and two backbones on protein expression levels using mRFP1, a red fluorescent protein, as a reporter. We found that a combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei with a backbone from pLEM415 yielded the highest level of reporter expression. When this construct was used to transform Lactobacillus casei, Lactobacillus delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in all these species and colonies of transformed Lactobacillus appeared pink under visible light. To test whether orally administered Lactobacillus can be retained in the GI tract of neonates, we fed the recombinant Lactobacillus casei to neonatal rats. We found that about 3% of the bacteria were retained in the GI tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus in the stomach and small intestine than in the cecum and colon. No mortality was observed throughout this study with Lactobacillus. In contrast, all neonatal rats died within 24 hours after fed with transformed E. coli. Taken together, our results indicate that Lactobacillus has the potential to be used as a vehicle for the delivery of therapeutic agents to neonates.     

Decreases in motor unit firing rate during sustained maximal-effort contractions in young and older adults

Previous studies have suggested that older adults may be more resistant to muscular fatigue than young adults. We sought to determine whether motor unit firing rate might be a factor that determines the response to fatiguing exercise in young and older subjects. Motor unit recordings and muscular forces were obtained from the tibialis anterior (TA) muscle of 11 young and 8 older individuals. Maximal voluntary force was first measured during maximal-effort dorsiflexion contractions. Each subject then performed a series of 15 maximal isometric contractions, with each contraction lasting 30 s. A 10-s rest period separated the fatiguing contractions. As a result of the fatiguing exercise, both subject groups demonstrated a significant loss in maximal force. The force decline was less in the older adults (20.4%) than in the young adults (33.8%). As expected, prior to muscle fatigue, maximal firing rates in the TA muscle were greater in the young (28.1 ± 5.8 imp/s) than in the older adults (22.3 ± 4.8 imp/s). The decrease in motor unit firing rate with fatigue was also greater in the young adults (34.9%), than in the older adults (22.0%). These results suggest that the greater fatigue-resistance exhibited by older individuals might be explained by the fact that the decline in motor unit firing rate during fatigue is greater in young persons than it is in older adults.     

Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn

The aim of this study was to investigate the expression of prostaglandin EP1 receptor within the ventrolateral periaqueductal grey (VL PAG). The role of VL PAG EP1 receptor in controlling thermonociception and rostral ventromedial medulla (RVM) activity in healthy and neuropathic rats was also examined. EP1 receptor was indeed found to be expressed within the VL PAG and co-localized with vesicular GABA transporter. Intra-VL PAG microinjection of ONO-DI-004, a selective EP1 receptor agonist, dose-dependently reduced tail flick latency as well as respectively increasing and decreasing the spontaneous activity of ON and OFF cells. Furthermore, it increased the ON cell burst and OFF cell pause. Intra-VL PAG prostaglandin E2 (PGE2) behaved similarly to ONO-DI-004. The effects of ONO-DI-004 and PGE2 were antagonized by intra-VL PAG L335677, a selective EP1 receptor antagonist. L335677 dose-dependently increased the tail flick latency and ongoing activity of the OFF cells, while reducing the ongoing ON cell activity. It also decreased the ON cell burst and OFF cell pause. In neuropathic rats using spare nerve injury (SNI) of the sciatic nerve model, EP1 receptor expression decreased in the VL PAG. However, ONO-DI-004 and L335677 were able to alter pain responses and ON and OFF cell activity, as they did in healthy animals. Collectively, these data show that within the VL PAG, EP1 receptor has a facilitatory effect on the nociceptive response and consistently affects RVM neuron activity. Thus, the blockade of EP1 receptor in the VL PAG leads to antinociception in neuropathic pain conditions, despite its down-regulation. The expression of EP1 receptor on GABAergic neurons is consistent with an EP1 receptor blockade-induced disinhibition of the antinociceptive descending pathway at VL PAG level.     

Hemispheric asymmetries in speech perception: sense, nonsense and modulations

Background

The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding ‘rapid temporal processing’.

Methodology

A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds.

Conclusions

Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features.     

Animal disease and human trauma: the psychosocial implications of the 2001 UK foot and mouth disease disaster

The 2001 UK foot and mouth disease (FMD) crisis is commonly understood to have been a nonhuman animal problem, an economic industrial crisis that was resolved after eradication. By using a different lens, a longitudinal ethnographic study of the health and social consequences of the epidemic, the research reported here indicates that 2001 was a human tragedy as well as an animal one. In a diary-based study, it can be seen that life after the FMD crisis was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Diverse groups experienced distress well beyond the farming community. Such distress remained largely invisible to the range of “official” inquiries into the disaster. That an FMD epidemic of the scale of 2001 could happen again in a developed country is a deeply worrying prospect, but it is to be hoped that contingency plans are evolving along with enhanced understanding of the human, animal, and financial cost.     

Extinction and recolonization of coastal megafauna following human arrival in New Zealand

Extinctions can dramatically reshape biological communities. As a case in point, ancient mass extinction events apparently facilitated dramatic new evolutionary radiations of surviving lineages. However, scientists have yet to fully understand the consequences of more recent biological upheaval, such as the megafaunal extinctions that occurred globally over the past 50 kyr. New Zealand was the world''s last large landmass to be colonized by humans, and its exceptional archaeological record documents a vast number of vertebrate extinctions in the immediate aftermath of Polynesian arrival approximately AD 1280. This recently colonized archipelago thus presents an outstanding opportunity to test for rapid biological responses to extinction. Here, we use ancient DNA (aDNA) analysis to show that extinction of an endemic sea lion lineage (Phocarctos spp.) apparently facilitated a subsequent northward range expansion of a previously subantarctic-limited lineage. This finding parallels a similar extinction–replacement event in penguins (Megadyptes spp.). In both cases, an endemic mainland clade was completely eliminated soon after human arrival, and then replaced by a genetically divergent clade from the remote subantarctic region, all within the space of a few centuries. These data suggest that ecological and demographic processes can play a role in constraining lineage distributions, even for highly dispersive species, and highlight the potential for dynamic biological responses to extinction.