Chestnut-crowned babbler calls are composed of meaningless shared building blocks

A core component of human language is its combinatorial sound system: meaningful signals are built from different combinations of meaningless sounds. Investigating whether non-human communication systems are also combinatorial is hampered by difficulties in identifying the extent to which vocalizations are constructed from shared, meaningless building blocks. Here we present a novel approach to circumvent this difficulty and show that a pair of functionally distinct chestnut-crowned babbler (Pomatostomus ruficeps) vocalizations can be decomposed into perceptibly distinct, meaningless entities that are shared across the two calls. Specifically, by focusing on the acoustic distinctiveness of sound elements using a habituation-discrimination paradigm on wild-caught babblers under standardized aviary conditions, we show that two multi-element calls are composed of perceptibly distinct sounds that are reused in different arrangements across the two calls. Furthermore, and critically, we show that none of the five constituent elements elicits functionally relevant responses in receivers, indicating that the constituent sounds do not carry the meaning of the call; so are contextually meaningless. Our work, which allows combinatorial systems in animals to be more easily identified, suggests that animals can produce functionally distinct calls that are built in a way superficially reminiscent of the way that humans produce morphemes and words. The results reported lend credence to the recent idea that language’s combinatorial system may have been preceded by a superficial stage where signalers neither needed to be cognitively aware of the combinatorial strategy in place, nor of its building blocks

The application and use of chemical space mapping to interpret crystallization screening results

Mapping crystallization results in chemical space helps to correlate seemingly distant relationships between crystallization conditions, points to possible optimization strategies and reveals promising unsampled areas of crystallization space

Structural and functional characterization of the oxidoreductase a-DsbA1 from wolbachia pipientis

The &alpha;-proteobacterium Wolbachia pipientis is a highly successful intracellular endosymbiont of invertebrates that manipulates its host\u27s reproductive biology to facilitate its own maternal transmission. The fastidious nature of Wolbachia and the lack of genetic transformation have hampered analysis of the molecular basis of these manipulations. Structure determination of key Wolbachia proteins will enable the development of inhibitors for chemical genetics studies. Wolbachia encodes a homologue (&alpha;-DsbA1) of the Escherichia coli dithiol oxidase enzyme EcDsbA, essential for the oxidative folding of many exported proteins. We found that the active-site cysteine pair of Wolbachia &alpha;-DsbA1 has the most reducing redox potential of any characterized DsbA. In addition, Wolbachia &alpha;-DsbA1 possesses a second disulfide that is highly conserved in &alpha;-proteobacterial DsbAs but not in other DsbAs. The &alpha;-DsbA1 structure lacks the characteristic hydrophobic features of EcDsbA, and the protein neither complements EcDsbA deletion mutants in E. coli nor interacts with EcDsbB, the redox partner of EcDsbA. The surface characteristics and redox profile of &alpha;-DsbA1 indicate that it probably plays a specialized oxidative folding role with a narrow substrate specificity. This first report of a Wolbachia protein structure provides the basis for future chemical genetics studies.<br /

Exploring the ‘middle ground’ between state and market: the example of China

Studies of housing systems lying in the ‘middle ground’ between state and market are subject to three important shortcomings. First, the widely used Esping-Andersen (EA) approach assesses only a subset of the key housing outcomes and may be less helpful for describing changes in housing policy regimes. Second, there is too much emphasis on tenure transitions, and an assumed close correspondence between tenure labels and effective system functioning may not be valid. Third, due attention has not been given to the spatial dimensions in which housing systems operate, in particular when housing policies have a significant devolved or localised emphasis. Updating EA’s framework, we suggest a preliminary list of housing system indicators in order to capture the nature of the housing systems being developed and devolved. We verified the applicability of this indicator system with the case of China. This illustrates clearly the need for a more nuanced and systematic basis for categorising differences and changes in welfare and housing policies

Cloning, expression, purification and characterization of a DsbA-like protein from Wolbachia pipientis

Wolbachia pipientis are obligate endosymbionts that infect a wide range of insect and other arthropod species. They act as reproductive parasites by manipulating the host reproduction machinery to enhance their own transmission. This unusual phenotype is thought to be a consequence of the actions of secreted Wolbachia proteins that are likely to contain disulfide bonds to stabilize the protein structure. In bacteria, the introduction or isomerization of disulfide bonds in proteins is catalyzed by Dsb proteins. The Wolbachia genome encodes two proteins, a-DsbA1 and a-DsbA2, that might catalyze these steps. In this work we focussed on the 234 residue protein a-DsbA1; the gene was cloned and expressed in Escherichia coli, the protein was purified and its identity confirmed by mass spectrometry. The sequence identity of a-DsbA1 for both dithiol oxidants(E. coli DsbA, 12%) and disulfide isomerases(E. coli DsbC, 14%) is similar. We therefore sought to establish whether a-DsbA1 is an oxidant or an isomerase based on functional activity. The purified a-DsbA1 was active in an oxidoreductase assay but had little isomerase activity, indicating that a-DsbA1 is DsbA-like rather than DsbC-like. This work represents the first successful example of the characterization of a recombinant Wolbachia protein. Purified a-DsbA1 will now be used in further functional studies to identify protein substrates that could help explain the molecular basis for the unusual Wolbachia phenotypes, and in structural studies to explore its relationship to other disulfide oxidoreductase proteins. Copyright © 2008 Elsevier In

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

ObjectiveShortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.MethodsHigh-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.ResultsUninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.ConclusionsMEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health

Functional Brain Abnormalities During Finger-Tapping in HIV-Infected Older Adults: A Magnetoencephalography Study

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35-70%. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice