IntroductionGlobal population ageing is one of the key factors linked to the projected rise of dementia incidence. Hence, there is a clear need to identify strategies to overcome this expected health burden and have a meaningful impact on populations’ health worldwide. Current evidence supports the role of modifiable dietary and lifestyle risk factors in reducing the risk of dementia. In South-East Asia, changes in eating and lifestyle patterns under the influence of westernised habits have resulted in significant increases in the prevalence of metabolic, cardiovascular and neurodegenerative non-communicable diseases (NCDs). Low vegetable consumption and high sodium intake have been identified as key contributors to the increased prevalence of NCDs in these countries. Therefore, nutritional and lifestyle strategies targeting these dietary risk factors are warranted. The overall objective of this randomised feasibility trial is to demonstrate the acceptability of a dietary intervention to increase the consumption of high-nitrate green leafy vegetables and reduce salt intake over 6 months among Malaysian adults with raised blood pressure.Methods and analysisPrimary outcomes focus on feasibility measures of recruitment, retention, implementation and acceptability of the intervention. Secondary outcomes will include blood pressure, cognitive function, body composition and physical function (including muscle strength and gait speed). Adherence to the dietary intervention will be assessed through collection of biological samples, 24-hour recall and Food Frequency Questionnaire. A subgroup of participants will also complete postintervention focus groups to further explore the feasibility considerations of executing a larger trial, the ability of these individuals to make dietary changes and the barriers and facilitators associated with implementing these changes.Ethics and disseminationEthical approval has been obtained from Monash University Human Research Ethics Committee and Medical Research and Ethics Committee of Malaysia. Results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences.ISRCTN47562685; Pre-results.

Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.

30Contact repulsion of growing axons is an essential mechanism for spinal nerve 31 patterning. In birds and mammals the embryonic somites generate a linear series of 32 impenetrable barriers, forcing axon growth cones to traverse one half of each somite 33 as they extend towards their body targets. This study shows that protein disulphide 34 isomerase provides a key component of these barriers, mediating contact repulsion 35 at the cell surface in half-somites. Repulsion is reduced both in vivo and in vitro by a 36 range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric 37 oxide/S-nitrosylation-dependent signal transduction pathway that regulates the 38 growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar 39 activity, and the enzyme is expressed at the surface of cultured human astrocytic 40 cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to 41 counteract and regulate aberrant nerve terminal growth. 43Introduction 44 Peripheral spinal nerves have a striking anatomical periodicity, or segmentation, 45 that reflects their necessary isolation from the segments of developing bone that will 46 form the vertebral column. This study sets out to identify the molecular basis of this 47 patterning. We find a critical role for the enzyme protein disulfide isomerase in 48 separating outgrowing axons from the somite cells that generate the vertebrae, and 49 provide evidence regarding the underlying mechanism. 50In avian and mammalian embryos, both outgrowing motor and sensory axons, and 51 migrating neural crest cells, encounter the periodic somites that flank both sides of 52 the neural tube (future spinal cord). Here they traverse preferentially the anterior (A, 53 rostral/cranial) -rather than posterior (P, caudal) -halves of each successive 54 2 somite 1-4 . For neural crest cells this preference has been shown to depend on 55 repulsive signalling in the P-half-somite by members of the Semaphorin/Neuropilin-56 and Ephrin/Eph protein families [5][6][7][8][9] . However the basis of axonal segmental 57 patterning has remained elusive. 58We previously identified contact repulsion as the main cellular mechanism 59 generating axonal patterning 10,11 . Sequential repulsion of outgrowing motor and 60 sensory axons in successive P-half-sclerotomes (future vertebrae) forces axons to 61 traverse the anterior (A/cranial) halves. We showed that extracts of chick embryo 62 somites cause growth cone collapse of both motor and sensory axons in vitro 10 , a 63 phenomenon that is widely used as a method for identifying molecules that regulate 64 growth cone motility 12,13 . Additionally we found that the lectins peanut agglutinin 65 (PNA) and jacalin bind selectively to the surface of P-half-sclerotome cells rather 66 than A-half-sclerotome cells 10,14 . Immobilized PNA can be used to deplete collapse 67 activity, and activity is recovered by lactose elution. Biochemical purification led to 68 the identification of two PNA-binding glycoprote...

No abstract