Auditory sensory memory and working memory processes in children with normal hearing and cochlear implants.

There can be wide variation in the level of oral/aural language ability that prelingually hearing-impaired children develop after cochlear implantation. Automatic perceptual processing mechanisms have come under increasing scrutiny in attempts to explain this variation. Using mismatch negativity methods, this study explored associations between auditory sensory memory mechanisms and verbal working memory function in children with cochlear implants and a group of hearing controls of similar age. Whilst clear relationships were observed in the hearing children between mismatch activation and working memory measures, this association appeared to be disrupted in the implant children. These findings would fit with the proposal that early auditory deprivation and a degraded auditory signal can cause changes in the processes underpinning the development of oral/aural language skills in prelingually hearing-impaired children with cochlear implants and thus alter their developmental trajectory

Sensory-specific satiety and flavor amplification of foods

The effect of flavor amplification on sensory-specfic satiety was investigated. Nineteen young adults (mean age = 25 years) and 19 elderly adults (mean age = 72 years) rated the sensory properties of six foods, and were then asked to consume normal-flavored or flavor-amplified strawberry yogurt until comfortably full. The participants then re-rated the sensory properties of the six foods. There were no cl differences in the amount of yogurt consumed in either age group. Moreover flavor-fortifying the yogurt had no effect on the amount consumed in either age group. The consumption of both yogurts caused a reduction in rated pleasantness of the yogurt among young adults, but no change in the rated pleasantness of the uneaten foods. However, the elderly did not show a decrease in the rated pleasantness of any of the foods contained in the taste trays This study indicates that sensations of sensory-specific satiety were significantly reduced in the elderly, and these sensations were not induced by the addition of strawberry flavor to the yogurt.

Multiplexing Sensory Molecules Map Protons Near Micellar Membranes

Hi-fi mapping: Multiplexing fluorescent sensors that simultaneously target proton concentration and polarity move to micellar nanospaces, self-regulate their positions, and report their pKa values and wavelengths, which are controlled by their local environments. Such sensory functions enable maps of proton gradients near micellar membranes to be drawn.

STAT3, p38 MAP Kinase and NF-{kappa}B Drive Unopposed Monocyte-dependent Fibroblast MMP-1 Secretion in Tuberculosis.

Tissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells. We investigated mechanisms regulating Mtb-induced collagenolytic activity in fibroblasts in vitro and in patients. Lung fibroblasts were stimulated with conditioned media from Mtb-infected monocytes (CoMTb). CoMTb induced sustained increased MMP-1 (74 versus 16 ng/ml) and decreased tissue inhibitor of metalloproteinase (TIMP)-1 (8.6 versus 22.3 ng/ml) protein secretion. CoMTb induced a 2.7-fold increase in MMP-1 promoter activation and a 2.5-fold reduction in TIMP-1 promoter activation at 24 hours (P = 0.01). Consistent with this, TIMP-1 did not co-localize with fibroblasts in patient granulomas. MMP-1 up-regulation and TIMP-1 down-regulation were p38 (but not extracellular signal–regulated kinase or c-Jun N-terminal kinase) mitogen-activated protein kinase–dependent. STAT3 phosphorylation was detected in fibroblasts in vitro and in tuberculous granulomas.STAT3 inhibition reduced fibroblast MMP-1 secretion by 60% (P = 0.046). Deletion of the MMP-1 promoter NF-B–binding site abrogated promoter induction in response to CoMTb. TNF-, IL-1ß, or Oncostatin M inhibition in CoMTb decreased MMP-1 secretion by 65, 63, and 25%, respectively. This cytokine cocktail activated the same signaling pathways in fibroblasts and induced MMP-1 secretion similar to that induced by CoMTb. This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-B, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients.

Sensory and intrinsic coordination of movement

A recently generalized theory of perceptual guidance (general tau theory) was used to analyse coordination in skilled movement. The theory posits that (i) guiding movement entails controlling closure of spatial and/or force gaps between effecters and goals, by sensing and regulating the tau s of the gaps (the time-to-closure at current closure rate), (ii) a principal way of coordinating movements is keeping the rs of different gaps in constant ratio (known as tau-coupling), and (iii) intrinsically paced movements are guided and coordinated by tau-coupling onto a tau-guide, tau(g), generated in the nervous system and described by the equation tau(g) = 0.5(t-T-2/t) where T is the duration of the body movement and t is the time from the start of the movement. Kinematic analysis of hand to mouth movements by human adults, with eyes open or closed, indicated that hand guidance was achieved by maintaining, during 80-85% of the movement, the tau-couplings tau(alpha)-tau(t) and tau(t)-tau(g), where tau(t) is tau of the hand-mouth gap, tau(alpha) is tau of the angular gap to be closed by steering the hand and tau(g) is an intrinsic tau-guide.

Language-universal Sensory Deficits in Developmental Dyslexia: English, Spanish, and Chinese

Studies in sensory neuroscience reveal the critical importance of accurate sensory perception for cognitive development. There is considerable debate concerning the possible sensory correlates of phonological processing, the primary cognitive risk factor for developmental dyslexia. Across languages, children with dyslexia have a specific difficulty with the neural representation of the phonological structure of speech. The identification of a robust sensory marker of phonological difficulties would enable early identification of risk for developmental dyslexia and early targeted intervention. Here, we explore whether phonological processing difficulties are associated with difficulties in processing acoustic cues to speech rhythm. Speech rhythm is used across languages by infants to segment the speech stream into words and syllables. Early difficulties in perceiving auditory sensory cues to speech rhythm and prosody could lead developmentally to impairments in phonology. We compared matched samples of children with and without dyslexia, learning three very different spoken and written languages, English, Spanish, and Chinese. The key sensory cue measured was rate of onset of the amplitude envelope (rise time), known to be critical for the rhythmic timing of speech. Despite phonological and orthographic differences, for each language, rise time sensitivity was a significant predictor of phonological awareness, and rise time was the only consistent predictor of reading acquisition. The data support a language-universal theory of the neural basis of developmental dyslexia on the basis of rhythmic perception and syllable segmentation. They also suggest that novel remediation strategies on the basis of rhythm and music may offer benefits for phonological and linguistic development.

Vascular stem cells and ischaemic retinopathies

Retinal ischaemic disorders such as diabetic retinopathy and retinal vein occlusion are common. The hypoxia-related stimuli from oxygen-deprived neural and glial networks can drive expression of growth factors and cytokines which induce leakage from the surviving vasculature and/or pre-retinal and papillary neovascularisation. If left untreated, retinal vascular stasis, hypoxia or ischaemia can lead to macular oedema or fibro-vascular scar formation which are associated with severe visual impairment, and even blindness. Current therapies for ischaemic retinopathies include laser photocoagulation, injection of corticosteroids or VEGF-antibodies and vitreoretinal surgery, however they carry significant side effects. As an alternative approach, we propose that if reparative intra-retinal angiogenesis can be harnessed at the appropriate stage, ischaemia could be contained or reversed. This review provides evidence that reperfusion of ischaemic retina and suppression of sight-threatening sequelae is possible in both experimental and clinical settings. In particular, there is emphasis on the clinical potential for endothelial progenitor cells (EPCs) to promote vascular repair and reversal of ischaemic injury in various tissues including retina. Gathering evidence from an extensive published literature, we outline the molecular and phenotypic nature of EPCs, how they are altered in disease and provide a rationale for harnessing the vascular reparative properties of various cell sub-types. When some of the remaining questions surrounding the clinical use of EPCs are addressed, they may provide an exciting new therapeutic option for treating ischaemic retinopathies. (C) 2011 Elsevier Ltd. All rights reserved.

T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells

T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14(ARF) and p21(WAF1/cip1). In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue. Oncogene (2010) 29, 3252-3262; doi: 10.1038/onc.2010.84; published online 29 March 2010