Investigation into Possible Differences in Salmonella Prevalence in the Peripheral Lymph Nodes of Cattle Derived from Distinct Production Systems and of Different Breed Types.

Previous research demonstrated significant variation in the prevalence of Salmonella in peripheral lymph nodes (LNs) of feedlot cattle and cull cows, with greater prevalence in feedlot cattle. Therefore, we performed experiments to investigate whether these differences in Salmonella prevalence in subiliac LNs are due to, or influenced by, breed, which in many respects is a proxy for the production system in which the animal is derived. Holstein steers are a by-product of dairy systems, and beef steers are an intended product of commercial beef operations. For the first experiment, Holstein and beef steers originating from the same feedlot and harvested on the same day were sampled. Of the 467 Holstein and 462 beef cattle LNs collected, 62.1% of Holstein and 59.7% of beef cattle samples harbored Salmonella (P = 0.46; qualitative culture), with 51.2 and 48.9% of samples containing quantifiable concentrations (P = 0.49), respectively. The concentration of Salmonella within the LN followed a decreasing trend over the collection period (May to October), averaging 1.4 log CFU/g of LN for both Holstein and beef cattle samples (P = 0.78). In a second experiment, we compared 100% Brahman cattle to their beef cattle counterparts, as we hypothesized that the resistance of Brahman cattle to insects may reduce Salmonella transmission via biting insects. Of the 42 Brahman and 31 beef cattle LNs collected, the concentration of Salmonella within the LN averaged 3.0 log CFU/g for Brahman cattle and 2.9 log CFU/g for beef cattle samples (P = 0.30). Using qualitative culture, we recovered Salmonella from 100% of LNs from Brahman cattle and 97% of beef cattle samples (P = 0.25). Results of this research indicate that the differences observed are not due to breed and are likely a function of age, immune function, or other factors yet to be identified. Understanding which cattle are more likely to harbor Salmonella within LNs will aid in targeting both pre- and postharvest intervention strategies.

Loss of prestin does not alter the development of auditory cortical dendritic spines.

Disturbance of sensory input during development can have disastrous effects on the development of sensory cortical areas. To examine how moderate perturbations of hearing can impact the development of primary auditory cortex, we examined markers of excitatory synapses in mice who lacked prestin, a protein responsible for somatic electromotility of cochlear outer hair cells. While auditory brain stem responses of these mice show an approximately 40 dB increase in threshold, we found that loss of prestin produced no changes in spine density or morphological characteristics on apical dendrites of cortical layer 5 pyramidal neurons. PSD-95 immunostaining also showed no changes in overall excitatory synapse density. Surprisingly, behavioral assessments of auditory function using the acoustic startle response showed only modest changes in prestin KO animals. These results suggest that moderate developmental hearing deficits produce minor changes in the excitatory connectivity of layer 5 neurons of primary auditory cortex and surprisingly mild auditory behavioral deficits in the startle response.

Post-transcriptional modifications in the small subunit ribosomal RNA from Thermotoga maritima, including presence of a novel modified cytidine.

Post-transcriptional modifications of RNA are nearly ubiquitous in the principal RNAs involved in translation. However, in the case of rRNA the functional roles of modification are far less established than for tRNA, and are subject to less knowledge in terms of specific nucleoside identities and their sequence locations. Post-transcriptional modifications have been studied in the SSU rRNA from Thermotoga maritima (optimal growth 80 degrees C), one of the most deeply branched organisms in the Eubacterial phylogenetic tree. A total of 10 different modified nucleosides were found, the greatest number reported for bacterial SSU rRNA, occupying a net of approximately 14 sequence sites, compared with a similar number of sites recently reported for Thermus thermophilus and 11 for Escherichia coli. The relatively large number of modifications in Thermotoga offers modest support for the notion that thermophile rRNAs are more extensively modified than those from mesophiles. Seven of the Thermotoga modified sites are identical (location and identity) to those in E. coli. An unusual derivative of cytidine was found, designated N-330 (Mr 330.117), and was sequenced to position 1404 in the decoding region of the rRNA. It was unexpectedly found to be identical to an earlier reported nucleoside of unknown structure at the same location in the SSU RNA of the archaeal mesophile Haloferax volcanii.

Inpatient versus other settings for detoxification for opioid dependence.

BACKGROUND: There are a complex range of variables that can influence the course and subjective severity of opioid withdrawal. There is a growing evidence for the effectiveness of a range of medically-supported detoxification strategies, but little attention has been paid to the influence of the setting in which the process takes place. OBJECTIVES: To evaluate the effectiveness of any inpatient opioid detoxification programme when compared with all other time-limited detoxification programmes on the level of completion of detoxification, the intensity and duration of withdrawal symptoms, the nature and incidence of adverse effects, the level of engagement in further treatment post-detoxification, and the rates of relapse post-detoxification. SEARCH STRATEGY: Electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 3, 2004); MEDLINE (January 1966-March 2004); EMBASE (January 1988-March 2004); PsycInfo (January 1967-March 2004); CINAHL (January 1982-March 2004). In addition the Current Contents, Biological Abstracts, Science Citation Index and Social Sciences Index were searched. SELECTION CRITERIA: Randomised controlled clinical trials comparing inpatient opioid detoxification (any drug or psychosocial therapy) with other time-limited detoxification programmes (including residential units that are not staffed 24 hours per day, day-care facilities where the patient is not resident for 24 hours per day, and outpatient or ambulatory programmes, and using any drug or psychosocial therapy). DATA COLLECTION AND ANALYSIS: All abstracts were independently inspected by two reviewers (ED & JI) and relevant papers were retrieved and assessed for methodological quality using Cochrane Reviewers' Handbook criteria. MAIN RESULTS: Only one study met the inclusion criteria. This did not explicitly report the number of participants in each group that successfully completed the detoxification process, but the published data allowed us to deduce that 7 out of 10 (70%) in the inpatient detoxification group were opioid-free on discharge, compared with 11 out of 30 (37%) in the outpatient group. There was very limited data about the other outcomes of interest. AUTHORS' CONCLUSIONS: This review demonstrates that there is no good available research to guide the clinician about the outcomes or cost-effectiveness of inpatient or outpatient approaches to opioid detoxification.

Scopolamine reduces sensitivity to auditory gaps in the rat, suggesting a cholinergic contribution to temporal acuity.

Prior research [Caine et al., 1981] suggested that scopolamine, a central cholinergic antagonist, may increase gap thresholds in young human listeners. If confirmed, an effect of scopolamine on gap detection might help to explain why both aged humans and aged laboratory animals have less sensitive temporal acuity on gap detection tests, as they may be presumed to have less effective cholinergic mechanisms. Here we measured the effect of scopolamine on gap detection in rats (n=8) using reflex modification audiometry, which depends on the fact that brief gaps in noise presented immediately prior to a loud noise inhibit the acoustic startle reflex. Scopolamine increased the gap threshold and reduced reflex inhibition produced by gaps that were presented at and beyond about 40 ms prior to the startle reflex, but not at shorter lead times. A peripheral antagonist had no effect at long lead times. These data indicate that central cholinergic mechanisms are involved in relatively high level perceptual processing of gaps. This conclusion is consistent with the hypothesis that temporal acuity may be compromised in the aged listener because of deficits in the efficacy of these central mechanisms.

Key residues approach to the definition of protein families and analysis of sparse family signatures.

We extend the concept of the motif as a tool for characterizing protein families and explore the feasibility of a sparse "motif" that is the length of the protein sequence itself. The type of motif discussed is a sparse family signature consisting of a set of N key residue positions (A1, A2...AN) preceded by gaps (G) thus G1A1G2A2. ...GNAN. Both a residue and gap can be variable. A signature is matched to a protein sequence and scored using a dynamic programming algorithm which permits variability in gap distance and residue type. Generating a signature involves identifying residues associated with points of contact in interactions between secondary structure elements. A raw signature consists of a set of positions with potential key structural roles sampled from a sequence alignment constructed with reference to this contact data. Raw signatures are refined by sampling different gap-residue pairs until the specificity of a signature for the family cannot be further improved. We summarize signatures for nine families of protein of diverse fold and function and present results of scans against the OWL protein sequence database. The implications of such signatures are discussed.

Information resources for the bioinformatician.

The collaborative computing project in biosequence and structure analysis (CCPII) was established to foster bioinformatics in the broad community and the UK research community in particular. A World-Wide Web site called 'The Bioinformatics Resource' has been created containing a comprehensive set of information resources of use to the bioinformatician. The activities of CCPII are complementary to other providers of molecular biology information such as the BIOSCI electronic communication forum, which was established to facilitate communication between professionals in the biological sciences.

Exploring protein domain structure.

The protein databank contains coordinates of over 10,000 protein structures, which constitute more than 25,000 structural domains in total. The investigation of protein structural, functional and evolutionary relationships is fundamental to many important fields in bioinformatics research, and will be crucial in determining the function of the human and other genomes. This review describes the SCOP and CATH databases of protein structure classification, which define, classify and annotate each domain in the protein databank. The hierarchical structure, use and annotation of the databases are explained. Other tools for exploring protein structure relationships are also described.

Alignment of a sparse protein signature with protein sequences: application to fold prediction for three small globulins.

A novel algorithm has been developed for scoring the match between an imprecise sparse signature and all the protein sequences in a sequence database. The method was applied to a specific problem: signatures were derived from the probable folding nucleus and positions obtained from the determined interactions that occur during the folding of three small globular proteins and points of inter-element contact and sequence comparison of the actual three-dimensional structures of the same three proteins. In the case of two of these, lysozyme and myoglobin, the residues in the folding nucleus corresponded well to the key residues spotted by examination of the structures and in the remaining case, barnase, they did not. The diagnostic performance of the two types of signatures were compared for all three proteins. The significance of this for the application of an understanding of the protein folding mechanisms for structure prediction is discussed. The algorithm is generic and could be applied to other user-defined problems of sequence analysis.

A behavioral study of temporal processing and visual persistence in young and aged rats.

Young rats were presented with light flash prepulses varying in duration from 1 to 128 ms, with light offset or light onset fixed at 70 ms prior to an acoustic startle stimulus (Experiment 1A), and, with single or paired 1-ms flashes, the 2nd (or only) flash given 100 to 500 ms before the startle, and 1 ms to 400 ms interflash intervals (Experiment 1B). Older rats (10 and 20 months old) received the same single and double flashes but with the maximum interflash interval extended to 1,500 ms (Experiment 2). Reflex inhibition increased with increased duration from 1 to 8 ms and decreased as light onset progressively exceeded 100 ms. Inhibition for both single and double flashes also declined for onset lead times beyond 100 ms, then increased for a double flash once the interflash interval exceeded 100 ms in young and middle-aged rats and 1,500 ms in the oldest rats. Peak inhibition was much reduced in the oldest rats at short lead times but was greater than that of younger rats at long lead times. These data suggest that aged rats process visual stimuli more slowly than younger rats and show poorer temporal acuity coupled with greater visual persistence.

The effect of spatial separation of signal and noise on masking in the free field as a function of signal frequency and age in the mouse.

Masking of low- (4 kHz) and high-frequency (25 kHz) signals by one-octave bandpass maskers either spatially coincident with the signal or contralateral to it was examined in mice, 4-6 and 20-22 months of age, in the free field. Signals were presented 120 ms prior to a startle stimulus and differences in their inhibition of the startle reflex, relative to startle stimulus alone trials, were used to measure the severity of masking. Inhibition was reduced or eliminated by spatially coincident noise for weak but not for relatively intense signals, providing the type of "loudness recruitment" effect characteristic of human listeners in similar stimulus conditions. The spatial separation of the signal and its masker relieved this maskinglike effect for the high-frequency pair in both young and old mice. In contrast there was no beneficial effect of the shift in spatial location for the low-frequency pair at either age. This finding of masking release for high- but not low-frequency stimuli supports the hypothesis that the sound shadow provided by the head and pinna would yield a favorable signal-to-noise level difference for a contralateral masker and an ipsilateral signal only at very high frequencies in the mouse. The presence of masking release in these old mice, a first generation hybrid strain with near-normal high-frequency hearing in ABR measures, agrees with reports that the masking release resulting from a similar manipulation in aged human listeners with minimal high-frequency hearing loss is the equal of that obtained in the young listener.

Changes in temporal acuity with age and with hearing impairment in the mouse: a study of the acoustic startle reflex and its inhibition by brief decrements in noise level.

Temporal acuity for brief gaps in noise was studied in mice of different ages (1-36 months) from strains with differing susceptibility to age-related hearing loss, using reflex modification audiometry. Prepulse inhibition of the acoustic startle reflex (ASR) increased with gap depth (GD: 10-40 dB in 70 dB SPL noise) and lead time (LT: 1-15 ms). The increase in inhibition with LT followed an exponential function in which the two parameters, asymptotic inhibition (AINH) and the time constant (tau), were both affected by GD. AINH rapidly declined from 1 to 6 and then to 18 months of age in C57BL/6J mice with progressively severe hearing loss, but first increased with maturation and then gradually declined beyond 6-12 months of age in CBA/CaJ and CBA x C57BL Fl-hybrid mice, which show no apparent change in sensory function at these ages. In contrast, tau was unaffected by hearing loss or by age, this suggesting that age-related changes in this form of temporal acuity occur because of a reduction in the efficiency with which gaps are centrally processed, not from any reduced ability to follow their rapid shift in noise level.

Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse.

The gap detection paradigm is frequently used in psychoacoustics to characterize the temporal acuity of the auditory system. Neural responses to silent gaps embedded in white-noise carriers, were obtained from mouse inferior colliculus (IC) neurons and the results compared to behavioral estimates of gap detection. Neural correlates of gap detection were obtained from 78 single neurons located in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed from single-unit gap functions and were found to be comparable, 1-2 ms, to the behavioral gap threshold (2 ms). There was no difference in MGTs for units in which both carrier intensities were collected. Single unit responses were classified based on temporal discharge patterns to steady-state noise bursts. Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by sustained units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were obtained for inhibitory neurons (x = 14 ms). Finally, the time-course of behavioral and neurophysiological gap functions were found to be in good agreement. The results of the present study indicate the neural code necessary for behavioral gap detection is present in the temporal discharge patterns of the majority of IC neurons.

Nimodipine at a dose that slows ABR latencies does not protect the ear against noise.

We tested the hypothesis that nimodipine, a dihydropyridine reported to increase blood flow, block calcium and potassium channels, and reduce ischemic damage, would alleviate noise-induced hearing loss. Young C57B1/6J mice were exposed to wide-band noise (2 min, 120 dB SPL), with ABR thresholds (4-50 kHz) determined before noise exposure, and from 1 h to 2 weeks afterwards. One group (n = 7) received nimodipine (30 mg/kg/day) in daily peanut butter food supplements beginning 24 h before exposure; the other group (n = 6) received peanut butter alone. In the pretest nimodipine significantly increased the latency of Wave P1 of the ABR (mean difference: 0.16 ms; P < 0.02), showing that calcium blockade depressed sensorineural efficiency, but ABR thresholds were not affected. Noise exposure produced a severe threshold loss that partially recovered in the first week after exposure, and then suffered a slight but significant loss in the second week. These effects were seen equally in both groups: nimodipine did not reduce the severity of the immediate hearing loss following noise exposure, nor did it benefit recovery.

An evaluation of correction factors applied to dose-area product meter readings for the use of sinus cones.

As a result of the refurbishment of a dedicated skull radiography unit (Siemens Orbix) a dose-area product (DAP) meter was fitted into the light beam diaphragm/X-ray collimating system. Following calibration of the DAP system for X-ray beams defined by the unit's integral rectangular and octagonal iris diaphragms, DAP correction factors were obtained for the clinical use of externally fitted sinus cones. Correction factors can be derived from a simple ratio of coned to unconed beam areas, and these agree well with measured correction factors. The simple ratio of areas factor may be used in clinical practice to reduce potential errors.

Facilitation and inhibition of the acoustic startle reflex in the rat after a momentary increase in background noise level.

Small increments in background noise were shown to increase the amplitude of a subsequently elicited acoustic startle reflex (ASR) in rats by as much as 100% under optimal conditions. Increment lead time (5-160 ms) and level (1.5-15 dB), initial noise level (30-70 dB), startle level (95-125 dB), number of test days (1-5), and drug condition (diazepam or saline ip) were varied in 6 experiments. Prepulse facilitation (PPF), measured by difference scores, was greatest for intermediate increments (3 dB) and lead times (20-40 ms) and was replaced by prepulse inhibition (PPI) for higher values, especially in the later test days. Diazepam reduced baseline ASR and diminished PPI, but it did not affect PPF. These data argue against hypotheses that attribute PPF of this sort to either temporal integration within the ASR pathways or to the elicitation of a nonspecific arousal reaction by the prepulse.

Effects of facial cooling on elderly and young subjects: interactions with breath-holding and lower body negative pressure.

1. The effects of convective facial cooling by cold air on arterial blood pressure, heart rate and finger blood flow and on the reflex interactions between facial cooling and respiratory and orthostatic cardiac reflexes have been examined in 28 young adults (20-39 years) and 17 elderly (66-78 years) volunteer subjects. 2. During 2 min facial cooling alone, bradycardia was smaller (P < 0.001) and reduction in finger blood flow smaller (P < 0.001) in elderly subjects than in young subjects. Increases in systolic blood pressure and mean arterial pressure were similar and diastolic pressure increased only in the young subjects. Systolic blood pressure and mean arterial pressure remained elevated in the elderly 1 min after facial cooling, but subsided in the young. 3. Arterial blood pressure increased more during a 30-s breath-hold in expiration than in inspiration (P < 0.001) in both groups, and this was exaggerated by breath-hold in expiration combined with facial cooling. The bradycardia produced by facial cooling and breath-holding in expiration was more pronounced in the young subjects than in the elderly (P < 0.002). 4. Interactions between facial cooling and orthostatic reflexes induced by lower-body negative pressure showed significantly different age-related linear trends. Facial cooling diminished the hypotension induced by lower-body negative pressure in both groups. Facial cooling had a greater effect in diminishing the lower-body negative pressure-induced tachycardia in the young than in the elderly. 5. The mechanism of alteration of the facial cooling response in elderly subjects could be largely impairment of arterial baroreflexes, particularly as a result of reduced cardiac vagal activity as well as impairment of cardiopulmonary reflexes with ageing.

Effects of haloperidol and SCH 23390 on acoustic startle in animals depleted of dopamine as neonates: implications for neuropsychiatric syndromes.

Animals depleted of dopamine (DA) in the neonatal period and tested in adulthood exhibit some similarities to patients with schizophrenia, including increased sensitivity to DA agonists, altered sensitivity to DA receptor antagonists, and abnormalities of the acoustic startle response (ASR). In this study, we examined the contributions of D1-like and D2-like DA receptors to ASR measures in animals depleted of DA as neonates. Male rat pups received intracerebroventricular injections of 6-hydroxydopamine (DA depleted) or its vehicle (controls) at 3 days of age. Animals underwent startle testing as adults (60-75 days of age) after administration of DA antagonists (haloperidol: 0.1 or 0.3 mg/kg, SCH 23390:0.01 or 0.05 mg/kg) with and without DA agonist administration (apomorphine 0.5 mg/kg). ASR amplitude and prepulse inhibition (PPI: percentage decrease in startle amplitude due to a low intensity prepulse) were measured. DA depleted animals showed increased ASR amplitude and reduced PPI compared to controls. Administration of D1-like or D2-like DA antagonists significantly reduced overall ASR and increased PPI in both control and DA depleted animals, with DA depleted animals showing a relatively greater sensitivity to the D1-like antagonist SCH 23390. Findings are discussed in terms of the role of residual DA in mediating ASR phenomena in depleted animals, differences between D1/D2 DA receptor mediation of ASR compared to other behaviors in DA depleted animals, and potential implications for neuropsychiatric syndromes such as schizophrenia.