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Major membrane proteins and lipoproteins as highly variable immunogenic surface components and strain-specific antigenic markers of Mycoplasma arthritidis.

Surface antigenic variation was investigated in Mycoplasma arthritidis, an agent that produces chronic arthritis in rats which shares several features with many mycoplasma-induced diseases and thus defines a well-characterized model system. Hyperimmune rabbit antisera (anti-ISR1, anti-PG6, anti-H606 and anti-158p10) to whole M. arthritidis organisms were used as immunological probes in Western immunoblots of four M. arthritidis prototype strains (ISR1, PG6, H606 and D263) and five rat-passaged substrains (ISR1p1, ISR1p7, ISR1p8, 158p10 and D263p1). Several prominent antigens were identified that varied in expression. By Triton X-114 phase fractionation and treatment of whole cells with trypsin and carboxypeptidase Y, these strain-variant antigens were shown to be integral membrane proteins with C-termini and portions of the polypeptide chains oriented outside the membrane. Western blot immunoscreening of a large number of randomly selected clonal isolates and well-established clonal lineages from stock cultures of M. arthritidis ISR1p7, 158p10, PG6 and H606 revealed an expanded repertoire of variant membrane proteins whose expression was subject to independent, reversible phase variation. Colony immunoblots of these clonal populations with a hyperimmune rabbit antiserum to a gel-purified variant membrane protein (P36) showed that this phase switching occurred at a high frequency (10(-4) to 10(-2) per generation). Detailed immunological and biochemical characterization of the phase-variant membrane proteins demonstrated that they are: (i) antigenically related or distinct; (ii) apparently specific to particular strain populations; (iii) proteins or lipoproteins; (iv) major immunogens of M. arthritidis, recognized by serum antibodies from convalescent rat; and (v) able to undergo variation in expression during in vivo passage. Thus, M. arthritidis possesses a complex system capable of creating large repertoires of cell surface phenotypes which may affect the multiple interactions of this organism with its host and dictate its potential as a successful infectious agent and pathogen.

Animals↗

Not of one mind: mental models of clinical practice guidelines in the Veterans Health Administration.

OBJECTIVE: The purpose of this paper is to present differences in mental models of clinical practice guidelines (CPGs) among 15 Veterans Health Administration (VHA) facilities throughout the United States. DATA SOURCES: Two hundred and forty-four employees from 15 different VHA facilities across four service networks around the country were invited to participate. Participants were selected from different levels throughout each service setting from primary care personnel to facility leadership. STUDY DESIGN: This qualitative study used purposive sampling, a semistructured interview process for data collection, and grounded theory techniques for analysis. DATA COLLECTION: A semistructured interview was used to collect information on participants' mental models of CPGs, as well as implementation strategies and barriers in their facility. FINDINGS: Analysis of these interviews using grounded theory techniques indicated that there was wide variability in employees' mental models of CPGs. Findings also indicated that high-performing facilities exhibited both (a) a clear, focused shared mental model of guidelines and (b) a tendency to use performance feedback as a learning opportunity, thus suggesting that a shared mental model is a necessary but not sufficient step toward successful guideline implementation. CONCLUSIONS: We conclude that a clear shared mental model of guidelines, in combination with a learning orientation toward feedback are important components for successful guideline implementation and improved quality of care.

Attitude of Health Personnel↗

Evolution of the Borrelia burgdorferi outer surface protein OspC.

The genes coding for outer surface protein OspC from 22 Borrelia burgdorferi strains isolated from patients with Lyme borreliosis were cloned and sequenced. For reference purposes, the 16S rRNA genes from 17 of these strains were sequenced after being cloned. The deduced OspC amino acid sequences were aligned with 12 published OspC sequences and revealed the presence of 48 conserved amino acids. On the basis of the alignment, OspC could be divided into an amino-terminal relatively conserved region and a relatively variable region in the central portion. The distance tree obtained divided the ospC sequences into three groups. The first group contained ospC alleles from all (n = 13) sensu stricto strains, the second group contained ospC alleles from seven Borrelia afzelii strains, and the third group contained ospC alleles from five B. afzelii and all (n = 9) Borrelia garinii strains. The ratio of the mean number of synonymous (dS) and nonsynonymous (dN) nucleotide substitutions per site calculated for B. burgdorferi sensu stricto, B. garinii, and B. afzelii ospC alleles suggested that the polymorphism of OspC is due to positive selection favoring diversity at the amino acid level in the relatively variable region. On the basis of the comparison of 16S rRNA gene sequences, Borrelia hermsii is more closely related to B. afzelii than to B. burgdorferi sensu stricto and B. garinii. In contrast, the phylogenetic tree obtained for the B. hermsii variable major protein, Vmp33, and 18 OspC amino acid sequences suggested that Vmp33 and OspC from B. burgdorferi sensu stricto strains share a common evolutionary origin.

Amino Acid Sequence↗

Comparative strain typing of Rhizobium leguminosarum bv. viciae natural populations.

372 natural isolates of Rhizobium leguminosarum bv. viciae, rescued from nodules of pea plants grown in an agricultural field in northern Italy, were analyzed by different methods. Three DNA-based fingerprinting techniques were lined up to compare their relative degree of resolution and possible advantages of each approach. The methods included (i) Eckhardt gel plasmid profiles, (ii) pulsed-field gel electrophoresis (PFGE) of genomic large fragment digests, and (iii) random amplified polymorphic DNA (RAPD) profiles, generated with arbitrary primers. The scheme also involved the isolation of a number of different isolates per nodule to estimate the level of intra-nodular variability. It was therefore possible to evaluate the frequency of double and multiple occupancies, and the proportion of the alternative profiles sharing the same nodule, generally resulting in a numerically dominant, main representative accompanied by a secondary one with a slightly different fingerprint. This finding revealed that the different profiles within a nodule are normally due to bacteria derived from the same single invader following genetic alterations possibly occurred during infection, e.g., by plasmid loss. The analysis of 31 nodules revealed 16 different patterns, representing the most frequently occurring nodulation-proficient isolates of the natural soil examined, five of which were found with frequencies around 15%. The sensitivity of the methods in differentiating isolates was compared. The relatedness of the different natural rhizobial isolates was investigated by densitometrical gel analysis of the fingerprints, allowing a comparison of the results. One of the most interesting conclusions was that the degree of information yielded by the plasmid gel profiling alone, carried out by simple visual inspection without software-aided analyses, was surprisingly high, as it enabled a placement of the isolates, whose accuracy, in terms of relatedness, was subsequently confirmed by each of the two genomic methods.

Bacterial Typing Techniques↗

Log-linear models for gene mapping with affected sib pair data.

In genome-wide screens of genetic marker loci, non-mendelian inheritance of a marker is taken to indicate its vicinity to a disease locus. Heritable complex traits are thought to be under the influence of multiple possibly interacting susceptibility loci yet the most frequently used methods of linkage and association analysis focus on one susceptibility locus at a time. Here we introduce log-linear models for the joint analysis of multiple marker loci and interaction effects between them. Our approach focuses on affected sib pair data and identical by descent (IBD) allele sharing values observed on them. For each heterozygous parent, the IBD values at linked markers represent a sequence of dependent binary variables. We develop log-linear models for the joint distribution of these IBD values. An independence log-linear model is proposed to model the marginal means and the neighboring interaction model is advocated to account for associations between adjacent markers. Under the assumption of conditional independence, likelihood methods are applied to simulated data containing one or two susceptibility loci. It is shown that the neighboring interaction log-linear model is more efficient than the independence model, and incorporating interaction in the two-locus analysis provides increased power and accuracy for mapping of the trait loci.

Alleles↗

Comparing outpatient and inpatient diabetes education for newly diagnosed pediatric patients.

PURPOSE: The purpose of this study was to compare the efficacy of outpatient vs inpatient programs on medical, cognitive, behavioral, and psychosocial outcomes. METHODS: Using three large, tertiary medical centers in the United States, the sample of 32 children newly diagnosed with diabetes and their parents were recruited. Children and parents who received outpatient education were compared with those who received inpatient education. The following outcome variables were compared: (1) rates of hospital readmissions and/or emergency room visits for either severe hypoglycemia or ketoacidosis, (2) knowledge, (3) sharing of responsibilities, (4) adherence, (5) family functioning, (6) coping, and (7) quality of life. RESULTS: In general, no statistically significant differences were found between the groups. A trend was noted in the outpatient group with regard to improved use of emergency precautions on the adherence measure, roles on the family functioning measure, maintaining family integration on the parental coping measure, and disposition on the children's coping instrument. CONCLUSIONS: Findings support the safety and efficacy of the outpatient program method.

Adolescent↗

Cluster randomized trial of an active, multifaceted information dissemination intervention based on The WHO Reproductive health library to change obstetric practices: methods and design issues [ISRCTN14055385].

BACKGROUND: Effective strategies for implementing best practices in low and middle income countries are needed. RHL is an annually updated electronic publication containing Cochrane systematic reviews, commentaries and practical recommendations on how to implement evidence-based practices. We are conducting a trial to evaluate the improvement in obstetric practices using an active dissemination strategy to promote uptake of recommendations in The WHO Reproductive Health Library (RHL). METHODS: A cluster randomized trial to improve obstetric practices in 40 hospitals in Mexico and Thailand is conducted. The trial uses a stratified random allocation based on country, size and type of hospitals. The core intervention consists of three interactive workshops delivered over a period of six months. The main outcome measures are changes in clinical practices that are recommended in RHL measured approximately a year after the first workshop. RESULTS: The design and implementation of a complex intervention using a cluster randomized trial design are presented. CONCLUSION: Designing the intervention, choosing outcome variables and implementing the protocol in two diverse settings has been a time-consuming and challenging process. We hope that sharing this experience will help others planning similar projects and improve our ability to implement change.

Female↗

Facial and cochlear nerve function after surgery of cerebellopontine angle meningiomas.

OBJECTIVE: Meningiomas of the cerebellopontine angle (CPA) share a common location, but their site of dural origin and their relationship to surrounding neurovascular structures of the CPA are variable. The clinical presentation and outcome after surgical resection are different because of the diversity of this tumor entity. We report on a series of 421 patients with CPA meningiomas, with special emphasis on the analysis of the preoperative and postoperative facial and cochlear nerve function in relation to the site of dural attachment and main tumor location in the CPA cistern. METHODS: Among 421 patients, the charts of 347 patients with complete clinical data, including the history and audiograms, imaging studies, surgical records, discharge letters, histological records, and follow-up records, were reviewed retrospectively. Data about preoperative and postoperative facial nerve function were available in 334 patients, and audiometric analysis was conducted in 333 patients. Patients with neurofibromatosis Type 2 were excluded from the study. RESULTS: There were 270 women and 77 men, with a mean age of 53.4 years (range, 17.6-84 yr). Among these patients, 32.9% of the tumors originated at the petrous ridge anterior to the inner auditory canal (IAC) (Group 1), 22.2% showed involvement of the IAC (Group 2), 20.2% were located superior to the IAC (Group 3), 11.8% were inferior to the IAC (Group 4), and 12.9% were posterior to the IAC, originating between the IAC and the sigmoid sinus (Group 5). Patients presented with disturbance of Cranial Nerves V-VIII, the lower cranial nerves, and ataxia, depending on the main tumor location. Tumor resection was performed through a suboccipital-retrosigmoidal approach in the semisitting position in 95% of the patients. A combined supratentorial-infratentorial presigmoidal approach was performed in 5%. Total tumor removal (Simpson Grade 1 and 2) was achieved in 85.9% and subtotal removal in 14.1%. The best initial postoperative facial and auditory nerve function was observed in tumors belonging to Groups 3 and 5. Recovery from preoperative deafness was observed in 1.8% of patients. On long-term follow-up, good facial nerve function (House-Brackmann Grade 1 or 2) was observed in 88.9% of patients. Hearing preservation among patients with preoperative functional hearing was documented in 90.8% on long-term follow-up. CONCLUSION: Although the outcome of facial and cochlear nerve function is different in CPA meningiomas, depending on the topographic classification of these tumors, preservation of the cochlear nerve is possible in every tumor group and should be attempted in every patient with CPA meningioma. It has to be kept in mind that recovery of hearing was also observed in patients with preoperative profound hearing deficits.

Adolescent↗

How anorexic-like are the symptom and personality profiles of aesthetic athletes?

PURPOSE: We tested the hypothesis that aesthetic athletes (AA) have anorexic-like eating attitudes and behaviors, share personality characteristics such as perfectionism and obsessiveness, and are at high risk of eating disorders. METHODS: We compared symptomatology, personality variables typical of anorexia nervosa, and lifetime eating disorder prevalence across four groups of Israeli women: 31 anorexics, 111 AA (mostly dancers), 68 nonaesthetic athletes (NAA), and 248 controls. All participants completed self-report measures of symptomatology, harm avoidance, perfectionism, obsessiveness, self-esteem, and self-rated facial attractiveness and were screened for eating disorders. Those screening positively were interviewed and diagnosed using the structured clinical interview for DSM-IV. RESULTS: Scores of the anorexic women differed from those of the three other groups in the expected direction on all variables. NAA scored similarly to controls, but had greater body satisfaction and less drive for thinness. Surprisingly, the AA did not differ from control women on any self-report measure. However, significantly more AA (11.7%) than NAA (5.8%) and controls (4.4%) had a lifetime diagnosis of eating disorder not otherwise specified (EDNOS). The eating attitudes and behavior of the 13 AA with a lifetime history of EDNOS fell intermediately between the anorexic women and the controls, whereas their personality profile resembled that of controls. CONCLUSIONS: Being a nonaesthetic female athlete in Israel appears to promote body esteem and offer some protection from a preoccupation with dieting. AA also appear to enjoy excellent psychological health; however, a subgroup has EDNOS and appears not to receive appropriate treatment for it. These results lend credibility to the existence of the diagnostic entity of anorexia athletica, proposed to be a subclinical, environmentally influenced eating disorder with a favorable prognosis.

Adolescent↗

An interlaboratory study on the use of steroid hormones in examining endocrine disruption.

In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among animals and laboratories, there has been no study to examine the between-laboratory variability in actual steroid measurements. Therefore, we initiated a study with white sucker collected from a site receiving pulp mill effluent, previously documented as having reduced steroid levels, to address this issue. Samples of plasma and media from in vitro gonadal incubations were delivered to eight outside laboratories with the ability to measure steroid hormones. These laboratories ranged from well-established fish endocrine laboratories to wildlife toxicology laboratories, which have recently implemented the methods to measure steroid hormones. In this study, we have considered both the absolute measure of steroid content between laboratories as well as the ability to discriminate between reference and exposed populations as important criteria when evaluating the utility of these measures. Of the eight outside laboratories conducting the analyses, six detected identical site differences in circulating levels of testosterone and 17beta-estradiol to those documented by our Burlington laboratory (ON, Canada). However, the absolute value of the steroid hormones measured in the plasma varied significantly (plasma testosterone 0.6-23.1 ng/ml, 17beta-estradiol 77.6-1782.7 pg/ml) with coefficients of variation of 70.4% and 60.3% respectively. Similar results were demonstrated for the measurement of steroid hormones in media following in vitro gonadal incubation. Although there was a fair amount of variability in the absolute measure of steroid hormone levels, we would predict a far greater coherence of interlaboratory results through the sharing of reagents and the use of a common methodology between laboratories. These results are very promising, providing evidence for the inclusion of steroid hormones in monitoring endocrine disruption in wildlife species.

Animals↗

[The present state of paediatric neurology in the Autonomous Community of Madrid: variability in the distribution of resources].

INTRODUCTION: Paediatric neurology (PN) lies halfway between neurology and paediatrics, with no official acknowledgment. It is therefore difficult to determine exactly how resources are shared out. AIMS: The aim of this study is to analyse the public resources devoted to PN in the different health care areas within the Autonomous Community of Madrid (ACM). MATERIALS AND METHODS: In May 2002 we carried out a survey among child neurologists (CN) from the 9 independent health care districts within the ACM. RESULTS: A total of 28 CN work for the public health service in the ACM, eight of whom are employed on a part time basis. Only 53% are owners. The ratio of CN per 100000 inhabitants (inhab.) is 0.55 (0.45 after correction for part time work). The figure varies from one area to another from 0.07 to 1 CN/100000 inhab. (1/12000 1/220000 children). Part time neurologists work in the outer districts of the ACM. In most areas it is difficult to carry out diagnostic tests and these become even complicated when the child is small and requires some anaesthetic procedure. Neuropsychological assessment is one of the basic evaluations performed in PN and this is not easily performed in most centres. CONCLUSIONS: The CN/100000 inhab. ratio in the ACM is lower than that commonly recommended. The distribution of resources varies greatly and does not match demographic criteria. Temporary and part time jobs are commonplace in the peripheral areas. It is difficult for most centres to perform diagnostic tests.

Data Collection↗

Genetic variability and relationships in mitochondrial DNA CO II gene sequence of red common carps in China.

Nucleotide sequence of Cytochrome coxidase subunit II (CO II) of mitochondrial DNA ( mtDNA) was analyzed from four populations of the red common carp (C. c. var. singuonensis, C. c. var. wananensis, C. c. var. wuyuanensis and C. c. var. color) as well as one population of wild common carp in China to detect their genetic variability and phylogenetic relationship. Nineteen nucleotide variable positions were detected in analyzed 607 bp length sequence and 15 haplotypes were defined among five populations,but only one shared haplotype was observed in C. c. var. singuonensis and C. c. var. color, respectively. The characteristic intrapopulation single nucleotide polymorphisms (SNP) were observed in 103th, 149th, 239th, 368th, 395th nucleotide position. The highest haplotypic diversity (h) and nucleotide diversity (pi) existed in C. c. var. wuyuanensis and the lowest exited in C. c. var. wananensis. The significant fixation indices (Fst) in most comparisons between populations were observed. The neighbor-joining trees from haplotypes and populations of red common carp indicated C. c. var singuonensis and C. c. var. color might have originated from one monophyletic group, while C. c. var. wananensis and C. c. var. wuyuanenesis might have originated from an independent evolutionary branch.

Animals↗

Phyllogenetically conserved epitopes of the keratin 8 polypeptide recognized by a novel set of monoclonal antibodies.

In an attempt to raise a set of monoclonal antibody (MAb) probes for the study of biology and diagnostic value of human keratin No. 8, a series of hybridomas was prepared and their characteristics investigated by immunohistochemistry and immunoblotting. The polypeptide specificities of individual MAbs ranged from monospecificity for keratin No. 8 (MAbs C-15, C-23, C-36, C-43, C-47, C-51, and C-61) up to the "pan-keratin" MAbs C-11 and C-66 recognizing a broad range of keratins. The target epitopes of the remaining 4 MAbs (C-10, C-22, C-50, C-69) appear to be shared by various pairs of keratin polypeptides. The immunohistochemical investigation of tissues and/or cultured cells from 10 animal species revealed considerable variability of the interspecies crossreactivity of individual MAbs. The target epitopes of 5 MAbs appear to be phyllogenetically conserved from man to Xenopus, 6 of 12 MAbs tested show reactivity with several mammalian species (but not chicken or Xenopus) and the MAb C-15 reacts with human and sheep keratin only. The data obtained demonstrate that at least 9, and possibly as many as 12, nonidentical epitopes of the human keratin 8 polypeptide can be distinguished by this set of antibodies. The results of the present study suggest that our MAbs represent a significant contribution to the list of reagents applicable in both research of intermediate filament (IF) biology and diagnostic histopathology.

Animals↗

The increasing proportion of men with low earnings in the United States.

This study has provided an examination of recent changes in the lower tail of the male earnings distribution. Data from the CPS for 1967 through 1978 were used to analyze the increasing proportion of male workers with annual and weekly earnings below a fixed low earnings threshold. Our central purpose was to assess the extent to which the growth in the probability of low earnings could be explained by the more salient changes in the structure of the male labor force over this period. To this end, logit analysis was used to examine the roles of education, experience, cyclical conditions, and cohort size in explaining variations in the probability of subthreshold earnings, conditional on experience and education. The estimates generally yielded the expected effects. However, the most important findings from our analysis concern the trends estimated net of education, experience, unemployment, and cohort size. These variables appear to explain satisfactorily the recent growth in the proportion of men with low earnings among those with at least sixteen years of education. For all other educational categories, our independent variables were unable to account for a major portion of the growth in the probability of low earnings. Our results supplement previous findings of positive trends for mean annual and weekly earnings net of a similar set of independent variables. Hence, we have provided substantial evidence of stagnation in the lower tail of the male earnings distribution--a stagnation not shared by the average worker nor fully explicable by education, experience, aggregate unemployment, or the entrance of the baby boom cohort into the labor market. Investigation of alternative explanations for this phenomenon, such as changes in female labor supply or the structure of labor demand, is clearly warranted.

Adolescent↗

Factors associated with morbidity and mortality in feedlot calves: the Bruce County beef project, year two.

The results of the second year of the project confirmed most of the major findings from the initial year. Feeding cornsilage, particularly as the major roughage in the first month after arrival was associated with excess mortality. Mixing of cattle from different sources and vaccinating against respiratory disease appeared to be the most important additional factors that increased mortality rates. Delaying vaccination at least two days postarrival may have prevented the negative effects of vaccination but only in calves fed cornsilage. Morbidity rates were highly variable among farms but were positively correlated with mortality rates and treatment costs. The occurrence of infectious thromboembolic meningoencephalitis appeared to share some of the same risk factors as mortality; whereas, urolithiasis did not. Water deprivation may be a risk factor in the occurrence of urolithiasis. Fibrinous pneumonia was again the most frequent cause of death. Relative to year one, infectious thromboembolic meningoencephalitis increased in frequency and only one death was attributed to bovine virus diarrhea.

Animal Feed↗

Identifiability of food components for cancer chemoprevention.

Epidemiological studies have consistently reported a reduction in risk for several cancer sites in relation to high consumption of vegetables and fruit. These findings stimulated further research aimed at identifying which compounds in fruit and vegetables are responsible for the reduction in cancer risk. Epidemiological and laboratory studies suggested that some micronutrients, particularly vitamin C, vitamin E, beta-carotene, selenium, magnesium and zinc, could reduce the risk of cancers of the oral cavity, lung, oesophagus and stomach, while dietary fibre was more specifically related to a reduced risk of colorectal cancer. However, the results of large randomized trials on various combinations of vitamins and minerals at supranutritional doses have so far failed to confirm this hypothesis or have found very weak effects. These results should stimulate profound re-thinking of the methods that led to the selection of specific molecules with potential chemopreventive action. From a methodological point of view, little attention has so far been given to four main limitations of nutritional epidemiology, which have direct bearing on the extrapolation of results from foods to food components. Measurements of micronutrient intakes through simple dietary questionnaires and current food composition tables lack precision and specificity. Micronutrient intakes are often highly correlated in nature because micronutrients tend to share the same food sources. Attribution of cancer risk to a single food constituent can be misleading if multicollinearity of dietary variables is not recognized. The etiological meaning of nutritional biomarkers is not straightforward because circulating levels of nutrients reflect not only dietary intake but also complex metabolic regulations. Studies have not considered the physical characteristics of foods, which are important determinants of physiological responses. Understanding the multidimensional nature of diet and of its relationship with different cancers is a major scientific challenge. Epidemiological studies combining detailed dietary questionnaires, appropriate food composition tables, multiple biomarkers, and appropriate statistical methods may provide better measurements of the relationships between cancer risk and specific dietary patterns and therefore contribute to the identification of food components with hitherto unforeseen potential interest for cancer prevention.

Anticarcinogenic Agents↗

Functional redundancy and gustatory development in bdnf null mutant mice

In the mouse nasopalate papilla and in the trenches of the foliate and vallate papillae, taste buds accumulated primarily during the first 2 weeks after birth. Null mutation for brain-derived neurotrophic factor caused extensive death of embryonic taste neurons, with the secondary outcome that most taste buds failed to form. However not all taste neurons died; functional redundancy rescued a variable number. The primary research objective was to identify the likely site of the taste neuron rescue factor that substituted for BDNF. In this quest taste bud abundance served as a useful gauge of taste neuron abundance. The proportion of taste buds that developed was variable and uncorrelated among the nasopalate, vallate, and foliate gustatory papillae within each bdnf null mutant mouse. Thus, in spite of shared IXth nerve innervation, the vallate and foliate papillae independently varied in residual gustatory innervation. This variation rules against the rescue of gustatory neurons by system-wide factors or by factors acting on the IXth ganglion or nerve trunk. Therefore it is likely that surviving BDNF-deprived taste neurons were stochastically rescued by a redundant neurotrophic factor at the level of the local gustatory epithelium. These findings broaden the classic expectation that target tissue supplies only a single neurotrophic factor that can sustain sensory (taste) neurons.

Journal Article↗

Functional redundancy and gustatory development in bdnf null mutant mice.

In the mouse nasopalate papilla and in the trenches of the foliate and vallate papillae, taste buds accumulated primarily during the first 2 weeks after birth. Null mutation for brain-derived neurotrophic factor caused extensive death of embryonic taste neurons, with the secondary outcome that most taste buds failed to form. However not all taste neurons died; functional redundancy rescued a variable number. The primary research objective was to identify the likely site of the taste neuron rescue factor that substituted for BDNF. In this quest taste bud abundance served as a useful gauge of taste neuron abundance. The proportion of taste buds that developed was variable and uncorrelated among the nasopalate, vallate, and foliate gustatory papillae within each bdnf null mutant mouse. Thus, in spite of shared IXth nerve innervation, the vallate and foliate papillae independently varied in residual gustatory innervation. This variation rules against the rescue of gustatory neurons by system-wide factors or by factors acting on the IXth ganglion or nerve trunk. Therefore it is likely that surviving BDNF-deprived taste neurons were stochastically rescued by a redundant neurotrophic factor at the level of the local gustatory epithelium. These findings broaden the classic expectation that target tissue supplies only a single neurotrophic factor that can sustain sensory (taste) neurons.

Accessory Nerve↗