Reversible developmental stasis in response to nutrient availability in the Xenopus laevis central nervous system.

Many organisms confront intermittent nutrient restriction (NR), but the mechanisms to cope with nutrient fluctuations during development are not well understood. This is particularly true of the brain, the development and function of which is energy intensive. Here we examine the effects of nutrient availability on visual system development in Xenopus laevis tadpoles. During the first week of development, tadpoles draw nutrients from maternally provided yolk. Upon yolk depletion, animals forage for food. By altering access to external nutrients after yolk depletion, we identified a period of reversible stasis during tadpole development. We demonstrate that NR results in developmental stasis characterized by a decrease in overall growth of the animals, a failure to progress through developmental stages, and a decrease in volume of the optic tectum. During NR, neural progenitors virtually cease proliferation, but tadpoles swim and behave normally. Introducing food after temporary NR increased neural progenitor cell proliferation more than 10-fold relative to NR tadpoles, and cell proliferation was comparable to that of fed counterparts 1 week after delayed feeding. Delayed feeding also rescued NR-induced body length and tectal volume deficits and partially rescued developmental progression defects. Tadpoles recover from developmental stasis if food is provided within the first 9 days of NR, after which access to food fails to increase cell proliferation. These results show that early stages of tadpole brain development are acutely sensitive to fluctuations in nutrient availability and that NR induces developmental stasis from which animals can recover if food becomes available within a critical window.

Epidemiology and whole genome sequencing of an ongoing point-source Salmonella Agona outbreak associated with sushi consumption in western Sydney, Australia 2015.

During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.

Sensitivity testing of trypanosome detection by PCR from whole blood samples using manual and automated DNA extraction methods.

Automated extraction of DNA for testing of laboratory samples is an attractive alternative to labour-intensive manual methods when higher throughput is required. However, it is important to maintain the maximum detection sensitivity possible to reduce the occurrence of type II errors (false negatives; failure to detect the target when it is present), especially in the biomedical field, where PCR is used for diagnosis. We used blood infected with known concentrations of Trypanosoma copemani to test the impact of analysis techniques on trypanosome detection sensitivity by PCR. We compared combinations of a manual and an automated DNA extraction method and two different PCR primer sets to investigate the impact of each on detection levels. Both extraction techniques and specificity of primer sets had a significant impact on detection sensitivity. Samples extracted using the same DNA extraction technique performed substantially differently for each of the separate primer sets. Type I errors (false positives; detection of the target when it is not present), produced by contaminants, were avoided with both extraction methods. This study highlights the importance of testing laboratory techniques with known samples to optimise accuracy of test results.

Changes in neuronal acetylcholinesterase gene expression and division of labor in honey bee colonies.

Division of labor in honey bee colonies is highlighted by adult bees making a transition at 2-3 wk of age from working in the hive to foraging for nectar and pollen outside. This behavioral development involves acquisition of new tasks that may require advanced learning capabilities. Because acetylcholinesterase (AChE) hydrolyzes acetylcholine, a major neurotransmitter associated with learning in the insect brain, we searched for changes in AChE expression in the brain during bee behavioral development. Biochemical aspects of the AChE protein were similar in foragers and "nurse" bees that work in the hive tending brood. However, catalytic AChE activity was significantly lower in foragers. Cloning of bee AChE cDNA enabled mRNA analysis, which demonstrated that the forager-related decrease in AChE activity was associated with decreased AChE mRNA levels. This was particularly apparent in the mushroom bodies, a brain region known to be involved with olfactory and visual learning and memory. In addition, treatment with the AChE-inhibitor metrifonate improved performance in an olfactory-learning assay. These findings demonstrate long-term, naturally occurring developmental downregulation of AChE gene expression in the bee brain, and suggest that this genomic plasticity can contribute to facilitated learning capabilities in forager bees.

Effects of acute treatment with 8-OH-DPAT and fluoxetine on aggressive behaviour in male song sparrows (Melospiza melodia morphna).

The role of serotonin in modulating male aggressive behaviour was investigated in male song sparrows, Melospiza melodia morphna, using two different serotonergic drugs, fluoxetine and 8-OH-DPAT. Fluoxetine is a selective serotonin reuptake inhibitor of the neuronal reuptake pump increasing synaptic concentrations of serotonin, and 8-OH-DPAT is a specific serotonin (5-HT1A) receptor agonist. The serotonergic control of aggression in passerines has not been previously investigated. We examined these behaviours within a controlled setting using a laboratory simulated territorial intrusion, with a hierarchical scale to quantify male-male aggressive behaviour. Utilizing this scale, we quantified the extent of male aggressive behaviour in two experiments. In experiment 1, song sparrows were given 100 micro l, s.c. injections of either fluoxetine (10 mg/kg) or 8-OH-DPAT (1 mg/kg). Experiment 2 was a dose-response study using three doses of 8-OH-DPAT (0.1, 1 and 10 mg/kg). In both studies, aggressive behaviour was measured 1 h after injection for 10 min in response to the presence of a novel male decoy combined with playback of conspecific song. Both drugs significantly reduced male aggressive behaviour, and 8-OH-DPAT did so in a dose-dependent manner. The effect of the two drugs upon general activity was also measured using infra-red perch hop detectors. Activity levels were not effected by either fluoxetine or 8-OH-DPAT at all of the respective doses, indicating that the reduction in aggressive behaviour was specific. These results demonstrate that, in a passerine species, the serotonergic system negatively regulates male-male aggressive behaviour. These results further demonstrate that aggression can be effectively studied in a laboratory setting and natural aggressive responses can be elicited using this method.

Regulation of galanin-like peptide gene expression by pituitary hormones and their downstream targets.

Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for regulation by pituitary hormones or their downstream targets in the rat. The expression of GALP mRNA in the arcuate nucleus was reduced by hypophysectomy as determined by in situ hybridization. However, this did not appear to be attributable to the loss of either gonadal or adrenal steroids because castrated, ovariectomized and adrenalectomized rats had GALP mRNA expression that was indistinguishable from their respective controls. Next, we investigated the effects of growth hormone deficiency on GALP mRNA expression by studying dwarf rats and found that GALP gene expression was not different between dwarf rats and controls. We found that thyroidectomy led to a significant reduction in GALP mRNA expression compared to intact controls, and thyroidectomized rats implanted with thyroxine pellets had GALP mRNA expression that was similar to intact controls. Thus, the reduction of GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a selective loss of thyroid hormone. We also found that the expression of GALP mRNA was increased in the neurohypophysis of lactating rats compared to nonlactating rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by lactation. This suggests that the induction of GALP gene expression in pituicytes is physiologically associated with activation of oxytocin and vasopressin secretion during lactation.

Training sentence production in agrammatism: implications for normal and disordered language.

This paper presents an overview of our work concerned with treatment of sentence production deficits seen in agrammatic (Broca's) aphasic individuals. Using a single-subject experimental research paradigm, we examined emergent sentence production patterns in a subset of Broca's subjects who evinced sentence production (and comprehension) deficits involving "complex" sentences in which noun phrases (NPs) have been moved out of their canonical positions. We used aspects of Chomsky's Principles and Parameters approach of Government Binding (GB) Theory (Chomsky, 1986, Chomsky & Lasnik, 1991), as well as findings from the psycholinguistic and neurolinguistic literature as a basis for selecting sentences entered into our experiments and for designing our intervention approach, in general. Subjects were trained to produce sentences which rely on NP-movement (i.e., passives) or WH-movement (i.e., wh-questions, object clefts)--sentences formed by applying the rule "Move-alpha" in which moved constituents leave behind a "trace" or "gap" of their movement. Training emphasized the lexical and syntactic properties (e.g., thematic role assignment, NP-movement) of target sentences. Throughout this training we carefully measured generalization to untrained sentences relying on similar movement operations and error patterns were examined as they evolved over time. Results of our work indicated not only improved sentence production abilities in all subjects under study, but also--in many cases--generalization of sentence production across linguistic lines. That is, training WH-movement structures (e.g., object clefts) improved production of untrained WH-movement constructions (e.g., wh-questions) that are very different in their s-structure representation; however, no effect of this training on NP-movement structures occurred. In addition, within the class of wh-questions, generative production across questions relying on argument (direct object NP) movement (i.e., what- and who-questions) occurred in the absence of generalization to wh-questions requiring movement from adjunct position (i.e., where- and when-questions) for some subjects. For others, generalized production occurred only when wh-morphemes were the focus of treatment, indicating that at least two processes must be completed for successful wh-question production to take place: movement of the wh-item itself and control of sublexical features that determine wh-morpheme selection. These data are discussed in terms of the contribution that detailed recovery data, controlled for lexical and syntactic properties of sentence production, can make both to understanding the nature of sentence production deficits and to issues regarding normal sentence production.

Patterns of comprehension and production of nouns and verbs in agrammatism: implications for lexical organization.

This study examined the relationship between verb retrieval and verb-argument-structure properties in seven agrammatic aphasic patients using tasks requiring access to the verb's lexicon for both comprehension- and productionlike processes. Results showed intact comprehension of both nouns and verbs and noun naming, but impaired naming of verbs. Subjects also demonstrated near-normal performance on a grammaticality judgment task involving verb-argument-structure violations but were impaired in categorizing verbs by type (based on number of obligatory arguments). In both naming and categorization conditions, a hierarchy of verb difficulty emerged. Subjects were more accurate in naming/categorizing one-place verbs than two-place verbs and more accurate in naming/categorizing two-place verbs than three-place verbs. The pattern of selective impairment in lexical access/retrieval supports the hypothesis that one dimension of normal lexical organization is by form class. The results also suggest that no necessary relationship exists between production difficulties and comprehension of nouns/verbs in agrammatism. Further, the performance pattern noted supports the claim that verb-argument-structure properties, an important component of the verb lexicon, influence verb production at the single-word and at the sentence level. Subjects' performance on different tasks suggests that the locus of breakdown in the verb-retrieval processes for productionlike tasks may be in accessing information at the lemma level of representation as per Bock's model (1995) of sentence production.

Effects of hypnosis and imagery training on naming behavior in aphasia.

The effects of hypnosis and imagery training on the naming behavior of three subjects with Broca's aphasia were investigated using a multiple baseline design across subjects. Treatment consisted of the induction of hypnosis, followed by guided imagery focused on the physical and functional attributes of stimulus objects. Measures of naming ability on both trained and untrained items were taken at baseline, after every training session, and a few hours after training each day. Measures were also taken of imagery ability, hypnotic susceptibility, and psychological state. Results indicated that treatment facilitated improvement in naming ability, over baseline level, for two subjects. In the case of the third subject, the verbal label was incorporated into the imagery procedure following 10 training sessions. Subsequently, this subject's naming behavior improved over baseline level. The results are discussed in terms of current theory and research in neuropsychology and cognitive psychology.

Training wh-question production in agrammatic aphasia: analysis of argument and adjunct movement.

The present research utilized aspects of the Principles and Parameters Approach (P&PA; Chomsky, 1991, 1993) in linguistic theory as well as findings from the psycholinguistic literature as a basis for examining sentence production in aphasic individuals. We examined the production of particular wh-movement constructions--wh-questions requiring movement of an argument noun phrase (i.e., who and what questions) and those which require adjunct movement (i.e., when and where questions). Using a single-subject experimental treatment paradigm, subjects were sequentially trained to produce these wh-questions and, throughout training, generalization to untrained wh-questions relying on similar wh-movement processes was tested. As well, the influence of training on aspects of narrative and conversational discourse was examined. Seven agrammatic aphasic subjects who evinced difficulty producing (and comprehending) "complex" sentences (e.g., passives, object relative clauses, wh-questions)--sentences that involve movement of noun phrases (NPs) out of their canonical positions, leaving behind a "trace" of that movement or "gap"--participated in the study. Subjects were trained to produce wh-questions by taking them through a series of steps emphasizing the lexical and syntactic properties (e.g., thematic role assignment, movement processes, and proper selection of wh-morpheme) of declarative sentence counterparts of target sentences. Results revealed improved sentence production abilities in all subjects under study in both constrained sentence production and, importantly, in discourse tasks. The argument/adjunct distinction was observed in the sentence production recovery patterns noted in six of the seven subjects. Three of the subjects evinced correct argument movement across trained and untrained question structures when wh-questions relying on argument movement were trained; similarly, for these subjects, training structures relying of adjunct movement resulted in improved adjunct movement. Three of the remaining four subjects who required additional treatment to alleviate their wh-morpheme selection deficits, too showed covariance between argument and adjunct movement structures with each type of movement emerging across structures in temporal sequence. We discuss these data in terms of the operations necessary to produce wh-questions, the importance of considering linguistic and psycholinguistic data when designing treatment programs for language disordered patients, and the contribution that detailed recovery data can make both to understanding the nature of sentence production deficits and to issues regarding normal sentence production.

Agrammatic aphasic subjects' comprehension of subject and object extracted Wh questions.

This study attempted to replicate the unusual wh question comprehension pattern of Hickok and Avrutin's (1996) subjects who showed an expected subject/object extraction asymmetry for which NP questions, but not for who questions. We also examined comprehension of what and which one questions, which are similar to who and which NP questions, respectively, and we examined passivized wh questions in order to test predictions of Grodzinsky's (1995) restrictive theory of trace deletion, the Trace-Based Account (TBA). Results, using both a figurine manipulation task and a picture pointing task, showed that only one of four agrammatic (Broca's) aphasic subjects showed the pattern reported by Hickok and Avrutin and that this pattern extended to comprehension of what and which one questions. One of the subjects showed subject/object asymmetry for all wh questions tested, as would be predicted by the original trace deletion hypothesis (Grodzinsky, 1984), and two subjects showed neither pattern. None of our subjects demonstrated ability to comprehend passivized wh questions as predicted by the TBA. We discuss our findings in terms of the lack of homogeneity of wh question comprehension among individuals with agrammatic aphasia and we explore alternatives to the syntactic explanation for differences between who and which NP question comprehension advanced by Hickok and Avrutin.

Treatment and generalization of complex sentence production in agrammatism.

The present study applies single-subject experimental design to examine (a) the acquisition and generalization of complex sentence production in agrammatism using Linguistic Specific Treatment (LST) and (b) the utility of syntactic theory in guiding hypotheses of treatment effects. LST trains construction and production of complex sentence structures. Four sentence types were selected for study: object clefts and object-extracted matrix and embedded questions (which are noncanonical with wh-movement), and embedded actives (which are canonical with no overt movement). All sentences contain overt material in the complementizer phrase (CP) of the syntactic tree. Three of five participants (1, 2, and 3) demonstrated generalization from object cleft treatment to production of matrix questions. Thus, LST was effective in improving their ability to generate less complex sentences with wh-movement. Once production of object clefts and matrix questions was acquired, all 5 participants demonstrated generalization from treatment to improved production of embedded questions and/or embedded actives. This generalization involved improved ability to generate embedded clausal structure to form complex sentences but continuing inability to express overt material in CP. Finally, direct treatment for embedded questions did not result in accurate production of embedded actives or vice versa. There were no trends across participants toward improved production of morphosyntactic behaviors in narrative. Persons 1, 2, and 3 showed generalization to increased informativeness and efficiency of expression and were judged by independent listeners to improve in content, coherence, and fluency of spontaneous production. The remaining two participants showed no change or a decline in performance in narrative language production (4 and 5, respectively). These participants demonstrated more severe Broca's aphasia at pretesting compared to Persons 1, 2, and 3, with greater impairments in auditory comprehension, naming, and reading. Etiology and size of lesion did not appear to account for the different behavioral patterns. This study supports the use of LST, which applies syntactic theory to predict patterns of generalization, as an effective treatment approach.

Model-based semantic treatment for naming deficits in aphasia.

An interactive activation model for picture naming was used to guide treatment of a semantic-level deficit in 4 individuals with aphasia and severe picture-naming problems. Participants exhibited a profile consistent with Broca's aphasia with severe naming deficits, part of which was attributable to a semantic impairment based on testing of the lexical system. A semantic-based treatment was used to train naming of nouns in two semantic categories using a single-participant multiple baseline across behaviors and participants. Additional treatment, which included orthographic and phonological information about target words, then was applied. Treatment responses and error patterns demonstrated that semantic treatment resulted in improved naming of both trained and untrained items for 2 of 4 participants. Two participants did not show improved naming until treatment emphasizing the phonological form of the word was provided. This study demonstrates the utility of using an interactive activation model to plan treatment based on levels of disruption in the lexical processing system.

Cross-modal generalization effects of training noncanonical sentence comprehension and production in agrammatic aphasia.

The cross-modal generalization effects of training complex sentence comprehension and complex sentence production were examined in 4 individuals with agrammatic Broca's aphasia who showed difficulty comprehending and producing complex, noncanonical sentences. Object-cleft and passive sentences were selected for treatment because the two are linguistically distinct, relying on wh-and NP movement, respectively (Chomsky, 1986). Two participants received comprehension training, and 2 received production training using linguistic specific treatment (LST). LST takes participants through a series of steps that emphasize the verb and verb argument structure, as well as the linguistic movement required to derive target sentences. A single-subject multiple-baseline design across behaviors was used to measure acquisition and generalization within and across sentence types, as well as cross-modal generalization (i.e., from comprehension to production and vice versa) and generalization to discourse. Results indicated that both treatment methods were effective for training comprehension and production of target sentences and that comprehension treatment resulted in generalization to spoken and written sentence production. Sentence production treatment generalized to written sentence production only; generalization to comprehension did not occur. Across sentence types generalization also did not occur, as predicted, and the effects of treatment on discourse were inconsistent across participants. These data are discussed with regard to models of normal sentence comprehension and production.

Training and generalized production of wh- and NP-movement structures in agrammatic aphasia.

The present research examines production of "complex" sentences, which involve movement of noun phrases (NPs), in 2 agrammatic aphasic subjects. According to linguistic theory (Chomsky, 1991, 1993), such sentences are derived using one of two movement operations, either wh- or NP-movement, subsumed under the general rule "move alpha." In this experiment recovery of both wh- and NP-movement derived sentences was investigated using a treatment research paradigm. Subjects were sequentially trained to produce either wh-movement (i.e., who questions, object clefts) or NP-movement (i.e., passives, subject-raising structures) derived sentences. Throughout training, generalization to untrained sentences relying on both types of movement was tested. The influence of training on aspects of narrative discourse also was examined. Results showed generalization patterns constrained to type of movement. Training wh-movement structures resulted in generalized production of untrained wh-movement structures without influencing production of NP-movement structures. Similarly, training of NP-movement structures resulted in generalization only to other sentence types also relying on NP-movement. Aspects of sentence production in narrative contexts also was improved with treatment. These data indicate that movement to an argument (A) position as in NP-movement is distinct from movement to a non-argument (A-bar) position, required in wh-movement. The site where movement terminates in the s-structure of noncanonical sentences appears to influence sentence production. These findings show that linguistic properties of sentences influence sentence production breakdown and recovery in aphasia.

An experimental analysis of treatment effects on consonant clusters and ambisyllabic consonants in two adults with developmental phonological problems.

The effect of treatment on errors in consonant clusters and in ambisyllabic consonants were investigated in two adults with histories of developmental phonological problems. Using a multiple baseline across behaviors, ambisyllabic consonant errors were treated in bisyllabic words and consonant cluster errors were treated in two different cluster classes. Results indicated that treatment, consisting of a sound-referenced rebus approach, affected change in production of trained words as well as generalization to untrained words for targeted behaviors.

Effects of feedback and self-monitoring on head trauma youths' conversation skills.

The effects of feedback and self-recording on the small group conversational behaviors of two head trauma youths were evaluated. Feedback involved providing clients a light signal corresponding to positive or negative social interactions. The self-monitoring procedure required that the clients flip a switch corresponding with their positive or negative interactions. An A1-B1-C1-A2-C2-B2 design in which the feedback phase (B) and self-monitoring phase (C) were alternated to control for order effects demonstrated the efficacy of both interventions. Performance gains were also shown to generalize to less structured situations, bringing the clients' level of positive responses into a range established with a social comparison group.

Hemodynamic response function in patients with stroke-induced aphasia: implications for fMRI data analysis.

Functional MRI is based on changes in cerebral microvasculature triggered by increased neuronal oxidative metabolism. This change in blood flow follows a pattern known as the hemodynamic response function (HRF), which typically peaks 4-6 s following stimulus delivery. However, in the presence of cerebrovascular disease the HRF may not follow this normal pattern, due to either the temporal signal to noise (tSNR) ratio or delays in the HRF, which may result in misinterpretation or underestimation of fMRI signal. The present study examined the HRF and SNR in five individuals with aphasia resulting from stroke and four unimpaired participants using a lexical decision task and a long trial event-related design. T1-weighted images were acquired using an MP-RAGE sequence and BOLD T2*-weighted images were acquired using Echo Planar Imaging to measure time to peak (TTP) in the HRF. Data were analyzed using Brain Voyager in four anatomic regions known to be involved in language processing: Broca's area and the posterior perisylvian network (PPN) (including Wernicke's area, the angular and supramarginal gyri) and right hemisphere homologues of these regions. The occipital area also was examined as a control region. Analyses showed that the TTP in three out of five patients in the left perisylvian area was increased significantly as compared to normal individuals and the left primary visual cortex in the same patients. In two other patients no significant delays were detected. We also found that the SNR for BOLD signal detection may by insufficient in damaged areas. These findings indicate that obtaining physiologic (TTP) and quality assurance (tSNR) information is essential for studying activation patterns in brain-damaged patients in order to avoid errors in interpretation of the data. An example of one such misinterpretation and the need for alternative data analysis strategies is discussed.