Mechanisms of axon guidance in the developing nervous system

The human brain assembles an incredible network of over a billion neurons. Understanding how these connections form during development in order for the brain to function properly is a fundamental question in biology. Much of this wiring takes place during embryonic development. Neurons are generated in the ventricular zone, migrate out, and begin to differentiate. However, neurons are often born in locations some distance from the target cells with which they will ultimately form connections. To form connections, neurons project long axons tipped with a specialized sensing device called a growth cone. The growing axons interact directly with molecules within the environment through which they grow. In order to find their targets, axonal growth cones use guidance molecules that can either attract or repel them. Understanding what these guidance cues are, where they are expressed, and how the growth cone is able to transduce their signal in a directionally specific manner is essential to understanding how the functional brain is constructed. In this chapter, we review what is known about the mechanisms involved in axonal guidance. We discuss how the growth cone is able to sense and respond to its environment and how it is guided by pioneering cells and axons. As examples, we discuss current models for the development of the spinal cord, the cerebral cortex, and the visual and olfactory systems. (c) 2005, Elsevier Inc.

Investigating the performance of MIMO systems from an electromagnetic perspective

Multiple input multiple output (MIMO) wireless systems use multiple element antennas (MEAs) tit the transmitter (TX) and the receiver (RX) in order to offer improved information rates (capacity) over conventional single antenna systems in rich scattering environments. In this paper, an example of a simple MIMO system is considered in which both antennas and scattering objects is are formed by wire dipoles. Such it system can be analyzed in the strict electromagnetic (EM) sense and its capacity can be determined for varying array size, interelement spacing, and distributions of scatterers. The EM model of this MIMO system can be used to assess the validity of single- or double-bounce scattering models for mixed line of sight (LOS) and non-line of sight (NLOS) signal-propagation conditions. (c) 2006 Wiley Periodicals, Inc.

Non-coding RNA

The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have function. Although it has been generally assumed that most genetic information is transacted by proteins, recent evidence suggests that the majority of the genomes of mammals and other complex organisms is in fact transcribed into ncRNAs, many of which are alternatively spliced and/or processed into smaller products. These ncRNAs include microRNAs and snoRNAs (many if not most of which remain to be identified), as well as likely other classes of yet-to-be-discovered small regulatory RNAs, and tens of thousands of longer transcripts (including complex patterns of interlacing and overlapping sense and antisense transcripts), most of whose functions are unknown. These RNAs (including those derived from introns) appear to comprise a hidden layer of internal signals that control various levels of gene expression in physiology and development, including chromatin architecture/epigenetic memory, transcription, RNA splicing, editing, translation and turnover. RNA regulatory networks may determine most of our complex characteristics, play a significant role in disease and constitute an unexplored world of genetic variation both within and between species.

Changes in head and neck position have a greater effect on elbow joint position sense in people with whiplash-associated disorders

Background: It has been shown that perception of elbow joint position is affected by changes in head and neck position. Further, people with whiplash-associated disorders (WAD) present with deficits in upper limb coordination and movement. Objectives: This study is aimed to determine whether the effect of changes in head position on elbow joint position error (JPE) is more pronounced in people with WAD, and to determine whether this is related to the participant's pain and anxiety levels. Methods: Nine people with chronic and disabling WAD and 11 healthy people participated in this experiment. The ability to reproduce a position at the elbow joint was assessed after changes in the position of the head and neck to 30 degrees, and with the head in the midline. Pain was monitored in WAD participants. Results: Absolute elbow JPE with the head in neutral was not different between WAD and control participants (P = 0.5). Changes in the head and neck position increased absolute elbow JPE in the WAD group (P < 0.05), but did not affect elbow JPE in the control group (P = 0.4). There was a connection between pain during testing and the effect of changes in head position on elbow JPE (P < 0.05). Discussion: Elbow JPE is affected by movement of the head and neck, with smaller angles of neck rotation in people with WAD than in healthy individuals. This observation may explain deficits in upper limb coordination in people with WAD, which may be due to the presence of pain or reduced range of motion in this population.

The sense of belonging to a neighbourhood: can it be measured and is it related to health and well being in older women?

This study investigates the sense of belonging to a neighbourhood among 9445 women aged 73-78 years participating in the Australian Longitudinal Study on Women's Health. Thirteen items designed to measure sense of neighbourhood were included in the survey of the older women in 1999. Survey data provided a range of measures of demographic, social and health-related factors to assess scale construct validity. Factor analysis showed that seven of the items loaded on one factor that had good face validity and construct validity as a measure of the sense of neighbourhood. Two of the remaining items related to neighbourhood safety and comprised a factor. A better sense of neighbourhood was associated with better physical and mental health, lower stress, better social support and being physically active. Women who had lived longer at their present address had a better sense of belonging to their neighbourhood, as did women living in non-urban areas and who were better able to manage on their income. Feeling safe in the neighbourhood was least likely in urban areas, increased in rural townships, and was most likely in rural and remote areas. Older women living alone felt less safe, as did women who were less able to manage on their income. This study has identified two sets of items that form valid measures of aspects of the social environment of older women, namely the sense of neighbourhood and feelings of safety. These findings make a contribution to our understanding of the relationship between feelings of belonging to a neighbourhood and health in older women. (C) 2004 Elsevier Ltd. All rights reserved.

Finding meaning in parenting a child with Asperger syndrome: correlates of sense making and benefit finding

This study explored the nature of two construals of meaning, benefit finding and sense making, in parents of a child with Asperger syndrome, and examined relations between both meaning constructs and the Double ABCX family stress model variables (initial stressor and pile-up of demands, appraisal, social support, coping strategies and adjustment) [H.I. McCubbin, J.M. Patterson, Social Stress and the Family: Advances and Developments in Family Stress Theory and Research, Haworth, New York, 1983, pp. 7-37]. A total of 59 parents completed questionnaires. Content analyses of parents' responses to questions inquiring about gains and sense making explanations revealed 8 benefit and 12 sense making themes. Results of correlations indicated that one or more of the meaning variables were related to each of the Double ABCX model predictors of parental adjustment. The meaning variables were positively related to adaptive coping processes: social support, self-efficacy, and problem-focused and emotional approach coping strategies. (C) 2004 Elsevier Ltd. All rights reserved.

Inhibition of in vitro VEGF expression and choroidal neovascularization by synthetic dendrimer peptide mediated delivery of a sense oligonucleotide

Ocular neovascularisation is the leading cause of blindness in developed countries and the most potent angiogenic factor associated with neovascularisation is vascular endothelial growth factor (VEGF). We have previously described a sense oligonucleotide (ODN-1) that possesses anti-human and rat VEGF activity. This paper describes the synthesis of lipid-lysine dendrimers and their subsequent ability to delivery ODN-1 to its target and mediate a reduction in VEGF concentration both in vitro and in vivo. Positively charged dendrimers were used to deliver ODN-1 into the nucleus of cultured D407 cells. The effects on VEGF mRNA transcription and protein expression were analysed using RT-PCR and ELISA, respectively. The most effective dendrimers in vitro were further investigated in vivo using an animal model of choroidal neovascularisation (CNV). All dendrimer/ODN-1 complexes mediated in a significant reduction in VEGF expression during an initial 24 hr period (40-60%). Several complexes maintained this level of VEGF reduction during a subsequent, second 24 hr period, which indicated protection of ODN-1 from the effects of endogenous nucleases. In addition, the transfection efficiency of dendrimers that possessed 8 positive charges (chi = 81(.)51%) was significantly better (P = 0(.)0036) than those that possessed 4 positive charges (chi = 56(.)8%). RT-PCR revealed a correlation between levels of VEGF protein mRNA. These results indicated that the most effective structural combination was three branched chains of intermediate length with 8 positive charges such as that found for dendrimer 4. Dendrimer 4 and 7/ODN-1 complexes were subsequently chosen for in vivo analysis. Fluorescein angiography demonstrated that both dendrimers significantly (P < 0(.)0001) reduced the severity of laser mediated CNV for up to two months post-injection. This study demonstrated that lipophilic, charged dendrimer mediated delivery of ODN-1 resulted in the down-regulation of in vitro VEGF expression. In addition, in vivo delivery of ODN-1 by two of the dendrimers resulted in significant inhibition of CNV in an inducible rat model. Time course studies showed that the dendrimer/ODN-1 complexes remained active for up to two months indicating the dendrimer compounds provided protection against the effects of nucleases. (C) 2004 Elsevier Ltd. All rights reserved.

The seeds of lotus japonicus lines transformed with sense, antisense, and sense/antisense galactomannan galactosyltransferase constructs have structually altered galactomannan in their endosperm cell walls

Galactomannan biosynthesis in legume seed endosperms involves two Golgi membrane-bound glycosyltransferases, mannan synthase and galactomannan galactosyltransferase (GMGT). GMGT specificity is an important factor regulating the distribution and amount of (1-->6)-alpha-galactose (Gal) substitution of the (1-->4)-beta-linked mannan backbone. The model legume Lotus japonicus is shown now to have endospermic seeds with endosperm cell walls that contain a high-Gal galactomannan (mannose [Man]/Gal = 1.2-1.3). Galactomannan biosynthesis in developing L. japonicus endosperms has been mapped, and a cDNA encoding a functional GMGT has been obtained from L. japonicus endosperms during galactomannan deposition. L. japonicus has been transformed with sense, antisense, and sense/antisense ("hairpin loop") constructs of the GMGT cDNA. Some of the sense, antisense, and sense/antisense transgenic lines exhibited galactomannans with altered (higher) Man/Gal values in their (T-1 generation) seeds, at frequencies that were consistent with posttranscriptional silencing of GMGT. For T-1 generation individuals, transgene inheritance was correlated with galactomannan composition and amount in the endosperm. All the azygous individuals had unchanged galactomannans, whereas those that had inherited a GMGT transgene exhibited a range of Man/Gal values, up to about 6 in some lines. For Man/Gal values up to 4, the results were consistent with lowered Gal substitution of a constant amount of mannan backbone. Further lowering of Gal substitution was accompanied by a slight decrease in the amount of mannan backbone. Microsomal membranes prepared from the developing T-2 generation endosperms of transgenic lines showed reduced GMGT activity relative to mannan synthase. The results demonstrate structural modification of a plant cell wall polysaccharide by designed regulation of a Golgi-bound glycosyltransferase.

Changes in head and neck position affect elbow joint position sense

Changes in the position of the head and neck have been shown to introduce a systematic deviation in the end-point error of an upper limb pointing task. Although previous authors have attributed this to alteration of perceived target location, no studies have explored the effect of changes in head and neck position on the perception of limb position. This study investigated whether changes in head and neck position affect a specific component of movement performance, that is, the accuracy of joint position sense (JPS) at the elbow. Elbow JPS was tested with the neck in four positions: neutral, flexion, rotation and combined flexion/rotation. A target angle was presented passively with the neck in neutral, after a rest period; this angle was reproduced actively with the head and neck in one of the test positions. The potential effects of distraction from head movement were controlled for by performing a movement control in which the head and neck were in neutral for the presentation and reproduction of the target angle, but moved into flexion during the rest period. The absolute and variable joint position errors (JPE) were greater when the target angle was reproduced with the neck in the flexion, rotation, and combined flexion/rotation than when the head and neck were in neutral. This study suggests that the reduced accuracy previously seen in pointing tasks with changes in head position may be partly because of errors in the interpretation of arm position.

Transmitting focussed B1 field and SENSE reconstruction using an 8-element transceive torso phased array coil

In this work, a new design concept in chest imaging for MRI application is presented. A focused, 8-element transceive torso phased array coil is designed to investigate transmitting focused B1 field deep within the torso to enhance signal intensity and use in conjunction with SENSE reconstruction technique. Hybrid FDTD/MOM method is used to accurately predict the RF behavior inside the human torso. The simulation results reported herein demonstrate the feasibility of the design concept which shows that B1 field focusing with SENSE reconstruction is achievable, and the 8-element transceive torso phased array coil has the advantage to be used in transmit and receive mode for optimum and fast chest imaging.