Audiovisual time perception is spatially specific

Our sensory systems face a daily barrage of auditory and visual signals whose arrival times form a wide range of audiovisual asynchronies. These temporal relationships constitute an important metric for the nervous system when surmising which signals originate from common external events. Internal consistency is known to be aided by sensory adaptation: repeated exposure to consistent asynchrony brings perceived arrival times closer to simultaneity. However, given the diverse nature of our audiovisual environment, functionally useful adaptation would need to be constrained to signals that were generated together. In the current study, we investigate the role of two potential constraining factors: spatial and contextual correspondence. By employing an experimental design that allows independent control of both factors, we show that observers are able to simultaneously adapt to two opposing temporal relationships, provided they are segregated in space. No such recalibration was observed when spatial segregation was replaced by contextual stimulus features (in this case, pitch and spatial frequency). These effects provide support for dedicated asynchrony mechanisms that interact with spatially selective mechanisms early in visual and auditory sensory pathways

Speech Cues Contribute to Audiovisual Spatial Integration

Speech is the most important form of human communication but ambient sounds and competing talkers often degrade its acoustics. Fortunately the brain can use visual information, especially its highly precise spatial information, to improve speech comprehension in noisy environments. Previous studies have demonstrated that audiovisual integration depends strongly on spatiotemporal factors. However, some integrative phenomena such as McGurk interference persist even with gross spatial disparities, suggesting that spatial alignment is not necessary for robust integration of audiovisual place-of-articulation cues. It is therefore unclear how speech-cues interact with audiovisual spatial integration mechanisms. Here, we combine two well established psychophysical phenomena, the McGurk effect and the ventriloquist's illusion, to explore this dependency. Our results demonstrate that conflicting spatial cues may not interfere with audiovisual integration of speech, but conflicting speech-cues can impede integration in space. This suggests a direct but asymmetrical influence between ventral ‘what’ and dorsal ‘where’ pathways

Effects of humidity, leaf wetness, temperature and light on conidial production by Phaeoisariopsis personata on groundnut

Conidial production by P. personata [Mycosphaerella berkeleyi] on groundnut was studied under controlled environment conditions. With constant RH, conidia were only produced above a threshold (94.5% RH) and there was a linear increase between 94.5 and 100% RH. Conidial production was less with continuous leaf wetness (resembling heavy dew) than with continuous (98-99%) RH, but it was similar with intermittent leaf wetness and intermittent (98-99%) RH (8 h at 70% RH each day). With alternate high (≥97% RH) and low humidity, daily conidial production depended both on the duration of high RH and on the low RH value. With 99% RH at night (12 h), night-time conidial production decreased with the previous daytime RH. After conidial production had started, small numbers of conidia were produced even when the RH was well below the threshold level (94.5%). Conidia were produced in continuous light when the photon flux density was 2 µmol/m²/s, but production was completely inhibited with 60 µmol/m²/s. With constant RH, more conidia were produced with a 12-h photoperiod than in continuous darkness. However, >75% of the conidia were produced in the dark. With continuous darkness, more conidia were produced during the night (18.00-06.00 h) than during the day, but this biological rhythm was overcome with a light-night/dark-day regime. With constant (98-99%) RH, there was a linear increase in conidial production with temp. between 10 and 28°C, and virtually no conidia were produced at 33°. The daily production of conidia increased with time for 2-6 d, depending on the treatment

Desire and Dread from the Nucleus Accumbens: Cortical Glutamate and Subcortical GABA Differentially Generate Motivation and Hedonic Impact in the Rat

Background: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. Methodology/Principal Findings: Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic ‘‘liking’ ’ or ‘‘disliking’ ’ by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste ‘‘liking’ ’ (at rostral sites) versus ‘‘disliking’ ’ (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation

A selective cyclic integrin antagonist blocks the integrin receptors α(v)β(3 )and α(v)β(5 )and inhibits retinal pigment epithelium cell attachment, migration and invasion

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a leading cause of blindness after failed retinal reattachment surgery. PVR is characterized by the proliferation, migration and contraction of retinal pigmented epithelial cells (RPE), and these cellular responses are influenced by the expression and function of integrin receptors. The effect of a cyclic integrin antagonist containing the amino acid sequence Arg-Gly-Asp-D-Phe-Val (RGDfV), specific for the integrin receptors α(v)β(3 )and α(v)β(5), was investigated on basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), and serum induced human RPE proliferation, migration, invasion and attachment to the extracellular matrix. Furthermore, the effects of bFGF and PDGF-BB regulated expression of integrins α(v)β(3 )and α(v)β(5 )on RPE cells was examined. METHODS: The effect of a cyclic integrin antagonist and a control peptide (0.01 μg/ml to 300 μg/ml) was investigated on serum or cytokine (bFGF or PDGF-BB pretreatment) induced human fetal RPE cell proliferation by H(3)-thymidine uptake. The effect of the cyclic integrin antagonist on RPE cell attachment onto different extracellular matrices (laminin, collagen IV, fibronectin), RPE cell invasion stimulated by PDGF-BB or serum, and migration stimulated by PDGF-BB, vascular endothelial growth factor (VEGF) or serum was explored. PDGF-BB and bFGF modulation of the integrin receptors α(v)β(3 )and α(v)β(5 )was evaluated by flow cytometry. RESULTS: The integrin antagonist did not inhibit DNA synthesis stimulated by serum, bFGF, or PDGF-BB treatment. RPE attachment onto fibronectin was inhibited in a concentration range of 1–10 μg/ml (p < 0.05). Attachment of the RPE cells onto collagen IV and laminin was inhibited in a range of 3–10 μg/ml (p < 0.05). Serum and PDGF-BB stimulated migration was inhibited by the cyclic integrin antagonist in a concentration range of 1–10 μg/ml (p < 0.05). Furthermore, the cyclic integrin antagonist inhibited PDGF-BB stimulated RPE cell invasion through fibronectin (3μg/ml: 66% inhibition, p < 0.001). In each of these experiments, the control peptides had no significant effects. PDGF-BB and bFGF pretreatment of RPE cells increased the expression of integrin receptors α(v)β(3 )(bFGF: 1.9 fold, PDGF-BB: 2.3 fold) and α(v)β(5 )(bFGF: 2.9 fold, PDGF-BB: 1.5 fold). CONCLUSION: A selective inhibition of the integrin receptors α(v)β(3 )and α(v)β(5 )through a cyclic integrin antagonist is able to inhibit RPE cell attachment, migration and invasion. Since these steps are of importance for the progression of PVR, a cyclic integrin antagonist should be further evaluated for the treatment of this disease

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I–II essential hypertension: a randomized, double-blind clinical study

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20–40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8–12 mg once daily by forced titration) in 622 Japanese patients with grade I–II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was −12.4 mm Hg in the azilsartan group and −9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: −2.6 mm Hg, 95% confidence interval (CI): −4.08 to −1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was −21.8 mm Hg and −17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: −4.4 mm Hg, 95% CI: −6.53 to −2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety

Specialist nursing and community support for the carers of people with dementia living at home: an evidence synthesis.

Specialist nurses are one way of providing support for family carers of people with dementia, but relatively little is known about what these roles achieve, or if they are more effective than roles that do not require a clinical qualification. The aim of this review was to synthesise the literature on the scope and effectiveness of specialist nurses, known as Admiral Nurses, and set this evidence in the context of other community-based initiatives to support family carers of people with dementia. We undertook a systematic review of the literature relating to the scope and effectiveness of Admiral Nurses and a review of reviews of interventions to support the family carers of people with dementia. To identify studies, we searched electronic databases, undertook lateral searches and contacted experts. Searches were undertaken in November 2012. Results are reported narratively with key themes relating to Admiral Nurses identified using thematic synthesis. We included 33 items relating to Admiral Nurses (10 classified as research) and 11 reviews evaluating community-based support for carers of people with dementia. There has been little work to evaluate specific interventions provided by Admiral Nurses, but three overarching thematic categories were identified: (i) relational support, (ii) co-ordinating and personalising support and (iii) challenges and threats to the provision of services by Admiral Nurses. There was an absence of clearly articulated goals and service delivery was subject to needs of the host organisation and the local area. The reviews of community-based support for carers of people with dementia included 155 studies but, in general, evidence that interventions reduced caregiver depression or burden was weak, although psychosocial and educational interventions may reduce depression in carers. Community support for carers of people with dementia, such as that provided by Admiral Nurses, is valued by family carers, but the impact of such initiatives is not clearly established

Complications after hip arthroplasty and the association with hospital procedure volume: A nationwide retrospective cohort study on 50,080 total hip replacements with a follow-up of 3 months after surgery

Background and purpose: It has been suggested that a higher procedure volume is associated with less complications af

Tracking down carbon inputs underground from an arid zone Australian calcrete.

Freshwater ecosystems play a key role in shaping the global carbon cycle and maintaining the ecological balance that sustains biodiversity worldwide. Surficial water bodies are often interconnected with groundwater, forming a physical continuum, and their interaction has been reported as a crucial driver for organic matter (OM) inputs in groundwater systems. However, despite the growing concerns related to increasing anthropogenic pressure and effects of global change to groundwater environments, our understanding of the dynamics regulating subterranean carbon flows is still sparse. We traced carbon composition and transformations in an arid zone calcrete aquifer using a novel multidisciplinary approach that combined isotopic analyses of dissolved organic carbon (DOC) and inorganic carbon (DIC) (δ13CDOC, δ13CDIC, 14CDOC and 14CDIC) with fluorescence spectroscopy (Chromophoric Dissolved OM (CDOM) characterisation) and metabarcoding analyses (taxonomic and functional genomics on bacterial 16S rRNA). To compare dynamics linked to potential aquifer recharge processes, water samples were collected from two boreholes under contrasting rainfall: low rainfall ((LR), dry season) and high rainfall ((HR), wet season). Our isotopic results indicate limited changes and dominance of modern terrestrial carbon in the upper part (northeast) of the bore field, but correlation between HR and increased old and 13C-enriched DOC in the lower area (southwest). CDOM results show a shift from terrestrially to microbially derived compounds after rainfall in the same lower field bore, which was also sampled for microbial genetics. Functional genomic results showed increased genes coding for degradative pathways-dominated by those related to aromatic compound metabolisms-during HR. Our results indicate that rainfall leads to different responses in different parts of the bore field, with an increase in old carbon sources and microbial processing in the lower part of the field. We hypothesise that this may be due to increasing salinity, either due to mobilisation of Cl- from the soil, or infiltration from the downstream salt lake during HR. This study is the first to use a multi-technique assessment using stable and radioactive isotopes together with functional genomics to probe the principal organic biogeochemical pathways regulating an arid zone calcrete system. Further investigations involving extensive sampling from diverse groundwater ecosystems will allow better understanding of the microbiological pathways sustaining the ecological functioning of subterranean biota

Single-cell RNA-sequencing resolves self-antigen expression during mTEC development

The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection.RM is supported by a PhD Fellowship from the Fundação para a Ciência e Tecnologia, Portugal (SFRH/ BD/51950/2012). XZ is supported by an Advanced Postdoc Mobility Fellowship from the Swiss National Science Foundation (SNSF, grant number P300P2_151352). Part of the work was performed during XZ’s visit to the Simons Institute for the Theory of Computing. TL is supported by the Academy of Finland (Decision 311081). The authors would like to thank Bee Ling Ng and the staff of the Cytometry Core Facility, and Stephan Lorenz and the staff of the Single Cell Genomics Core Facility for their contribution. Mark Lynch is acknowledged for technical assistance with the Fluidigm C1 platform. Mike Stubbington and Kylie James are acknowledged for revising the language of the manuscript. We thank Sarah Teichmann for help and discussions regarding the manuscript.info:eu-repo/semantics/publishedVersio