Tomato (Lycopersicon esculentum) fruit ripening is initiated by an increase in ethylene hormone concentration. E8 gene transcription fruit-specific and activated at the onset of unripe treated with exogenous ethylene. To understand how controlled during ripening, we analyzed effect deletions flanking DNA sequences on expression transgenic tomato fruit. We found that a minimum three 5' one 3' regions influence ripening. confer responsiveness to are distinct from sufficient for

Abstract The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One the more severe infantile forms disease (INCL CLN1 disease) is due to mutations in palmitoyl-protein thioesterase 1 ( PPT1 ) gene severely reduces child’s lifespan approximately 9 years age. In order better translate human condition than possible mice, we sought produce large animal...

Increasing evidence suggests synaptic dysfunction is a central and possibly triggering factor in Amyotrophic Lateral Sclerosis (ALS). Despite this, we still know very little about the molecular profile of an ALS synapse. To address this gap, designed proteomics experiment to perform unbiased assessment proteome brain. We isolated synaptoneurosomes from fresh-frozen post-mortem human cortex (11 controls 18 ALS) stratified group based on cognitive (Edinburgh Cognitive Behavioural Screen (ECAS...

Abstract Spinal Muscular Atrophy is an autosomal dominant disease caused by mutations and deletions within the SMN1 gene, with predominantly childhood onset. Although primarily a motor neuron disease, defects in non-neuronal tissues are described both patients mouse models. Here, we have undertaken detailed study of heart Smn2B/− models SMA, reveal thinning ventriclar walls as previously more severe SMA. However most structural changes resolved accounting for smaller body size SMA mouse, was...

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed limited therapeutic time window systemic aspects of the disease. This raises fundamental question whether SMA has presymptomatic, developmental components to pathogenesis. We addressed this combining micro-computed tomography (μCT) comparative proteomics examine pre-symptomatic changes...

Using nationally representative data from 13 sub-Saharan African countries, we reinforce and expand upon previous findings that men report using condoms more frequently than women do unmarried respondents they use with casual partners married individuals them their spouses. Based on descriptive, bivariate, multivariate analyses, also demonstrate to a degree not previously shown in the current literature most countries extramarital about as partners. Married of included study reported less...

The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, both patients and animal models these diseases, not all equally vulnerable, that while some lost very early disease, others remain comparatively intact, even at late stages. This creates valuable system to investigate factors regulate vulnerability. In this study, we aim use experimental paradigm identify potential transcriptional modifiers. We have...

Separated, divorced, and widowed individuals in Africa are at significantly increased risk for HIV infection. Using nationally representative data from 13 sub-Saharan African countries, this study confirms that finding goes further by examining those who have experienced a marital dissolution now remarried. Results show remarried form large portion of the population higher-than-average prevalence. HIV-positive transmitting infection to their spouse, because many couples serodiscordant. The...

In this work, the features of fracture surfaces graphite-epoxy specimens as seen by both optical and scann ing electronic microscope (SEM) are presented. A variety test conditions were investigated. They are: tension (quasi- static), compression (quasi-static), tension-tension fatigue. Failure due to delamination was also studied (Mode I-Peel Testing). The sequence events leading failure monitored using an X-ray technique with opaque additive for image enhancement. After mechanical testing,...

Spinal muscular atrophy (SMA) is a devastating infantile genetic disorder caused by the loss of survival motor neuron (SMN) protein that leads to premature death due neurons and muscle atrophy. The approval an antisense oligonucleotide therapy for SMA was important milestone in research; however, effective next-generation therapeutics will likely require combinatorial SMN-dependent SMN-independent disease modifiers. A recent cross-disease transcriptomic analysis identified Stathmin-1...

Abstract Spinal muscular atrophy (SMA) is a childhood motor neuron disease caused by anomalies in the SMN1 gene. Although therapeutics have been approved for treatment of SMA, there therapeutic time window, after which efficacy reduced. Hallmarks unit pathology SMA include loss motor-neurons and neuromuscular junction (NMJs). Following an increase Smn levels, it unclear how much damage can be repaired degree to normal connections are re-established. Here, we perform detailed analysis before...

Synapses are a primary pathological target in neurodegenerative diseases. Identifying therapeutic targets at the synapse could delay progression of numerous conditions. The mitochondrial protein SFXN3 is neuronally enriched expressed synaptic terminals and regulated by key proteins, including α‐synuclein. We first show that uses carrier import pathway to insert into inner membrane. Using high‐resolution proteomics on Sfxn3 ‐KO mice synapses, we then demonstrate influences proteins pathways...

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease causing distal limb muscle that progresses proximally and accompanied by diaphragmatic paralysis. Neuromuscular junction (NMJ) alterations have been reported in muscles of SMARD1 model mice, known as nmd varying degrees severity, suggesting different are specifically selectively resistant or susceptible to denervation. To evaluate the extent NMJ pathology a broad range muscles,...

Neurodegenerative and neuromuscular disorders can manifest throughout the lifespan of an individual, from infant to elderly individuals. Axonal synaptic degeneration are early critical elements nearly all human neurodegenerative diseases neural injury, however molecular mechanisms which regulate this process yet be fully elucidated. Furthermore, how governing impacted by age individual is poorly understood. Interestingly, in mice under 3 weeks age, axons synapses following hypoxic or...

Abstract Quantification of immunohistochemically ( IHC ) labelled tissue sections typically yields semi‐quantitative results. Visualising infrared IR ‘tags’, with an appropriate scanner, provides alternative system where the linear nature fluorophore emittance enables realistic quantitative fluorescence QFIHC ). Importantly, this new technology entire to be scanned, allowing accurate area and protein abundance measurements calculated from rapidly acquired images. Here, some potential...

Abstract CLN1 disease is a fatal inherited neurodegenerative lysosomal storage of early childhood, caused by mutations in the gene, which encodes enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology Ppt1-deficient ( Ppt1 −/− ) mice and human that contributes to clinical outcome precedes onset brain pathology. Here, we quantified this at 3 7 months age revealing progressive glial activation vulnerability interneurons. Tandem mass tagged proteomic...

Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) has focused on SMA I. Here, proteomic profiling skin fibroblasts from severe (SMA I), intermediate II), and mild III) patients, alongside age-matched controls, was conducted using SWATH mass spectrometry analysis. Differentially expressed profiles showed limited overlap across each type, variability greatest within II fibroblasts, which not explained by SMN2 copy number. Despite overlap, enriched...

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that causes progressive muscle weakness and the leading genetic cause of infant mortality worldwide. SMA caused by loss survival motor neuron 1 ( SMN1 ). In humans, a nearly identical copy gene present, called SMN2 . Although maintains same coding sequence, this cannot compensate for because single silent nucleotide difference in exon 7. primarily produces alternatively spliced isoform lacking 7,...

In this experiment, the method of phase spectral analysis was used to monitor ultrasonic moduli changes in a two part epoxy adhesive bonded between steel adherends during cure as well cyclic loading. Ultrasonic signals were generated using piezoelectric transducer operated pulse-echo mode. These digitized high-speed transient digitizer (100 MHz sampling rate) and stored for post-test memory minicomputer. Based on information, attenuation velocity measurements (as function frequency) obtained...