Temporal profiling of the cortical synaptic mitochondrial proteome identifies ageing associated regulators of stability

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo

An optimized comparative proteomic approach as a tool in neurodegenerative disease research.

Recent advances in proteomic technologies now allow unparalleled assessment of the molecular composition of a wide range of sample types. However, the application of such technologies and techniques should not be undertaken lightly. Here, we describe why the design of a proteomics experiment itself is only the first step in yielding high-quality, translatable results. Indeed, the effectiveness and/or impact of the majority of contemporary proteomics screens are hindered not by commonly considered technical limitations such as low proteome coverage but rather by insufficient analyses. Proteomic experimentation requires a careful methodological selection to account for variables from sample collection, through to database searches for peptide identification to standardised post-mass spectrometry options directed analysis workflow, which should be adjusted for each study, from determining when and how to filter proteomic data to choosing holistic versus trend-wise analyses for biologically relevant patterns. Finally, we highlight and discuss the difficulties inherent in the modelling and study of the majority of progressive neurodegenerative conditions. We provide evidence (in the context of neurodegenerative research) for the benefit of undertaking a comparative approach through the application of the above considerations in the alignment of publicly available pre-existing data sets to identify potential novel regulators of neuronal stability

Initial Feasibility of a Woman-Focused Intervention for Pregnant African-American Women

African-American women who use crack are vulnerable to HIV because of the complex social circumstances in which they live. Drug-abuse treatment for these women during pregnancy may provide time for changing risk behaviors. This paper examines the initial 6-month feasibility of a women-focused HIV intervention, the Women's CoOp, adapted for pregnant women, relative to treatment-as-usual among 59 pregnant African-American women enrolled in drug-abuse treatment. At treatment entry, the women were largely homeless, unemployed, practicing unsafe sex, and involved in violence. Results indicated marked reductions in homelessness, use of cocaine and illegal drugs, involvement in physical violence, and an increase in knowledge of HIV from baseline to 6-month followup for both conditions. Findings suggest that the Women's CoOp intervention could be successfully adapted to treat this hard-to-reach population. Future studies should examine the efficacy of the pregnancy-adapted Women's CoOp for women not enrolled in drug-abuse treatment

Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases

The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers, and demonstrated SNCA is a modifier of pathology in motor neuron disease

Differences in Nursery Pigs’ Behavior on the Day of Vaccination

Swine industry feed suppliers are continually striving to develop techniques and tools to reduce the additive stressors imposed on the weanling piglet, to increase advantageous behaviors (feeding and drinking) and to reduce aggressive interactions. One product on the market designed to ease the transition from a liquid diet (sow\u27s milk) to a dry ration is a gel-based feed supplement that was incorporated in this trial as a means to positively affect feeding and drinking behaviors. The objectives of this study were to determine if there were differences in the nursery pigs’ behavior on the day of vaccination when provided a gel supplement. A total of 29 d crossbred pigs (5.94 kg) were housed in Double L® confinement nursery buildings. Four treatments were compared. No vaccine and no gel (control n = 4) defined as unvaccinated and without supplemental gel at days 8 to 10. No vaccine and gel (n = 4) defined as pigs that were provided supplemental gel at days 8 to 10 without vaccination. Vaccinated and no gel (n = 4) defined as pigs that were vaccinated but did not receive supplemental gel at days 8 to 10. Vaccinated and gel (n = 4) defined as pigs that were provided supplemental gel at days 8 to 10 and were vaccinated. The group of four pigs housed together in a pen was considered the experimental unit for data analysis. Definitions for the behaviors and postures recorded and summarized for the trial included the following: Active was defined as standing, this included any upright postures. Inactive posture was defined as sitting or lying postures (both lateral and sternal). Time at drinker was defined as when an individual pig’s mouth was around the water nipple. Time at feeding stations was defined as the time when the individual pig’s head was inside the creep (that contained gel) or the three hole feeder (dry pelleted feed). Nursery aged pigs were less active (P \u3c 0.05; Figure 1) and spent less time (P \u3c 0.05; Figure 2) at the feeding stations 1- h after receiving Mycoplasma hyopneumoniae vaccination, indicating a short term behavioral response to this stressor. These behavioral alterations continued for approximately 6- h (or 5:00 PM the vaccination day afternoon). After this time, all nursery pigs regardless of treatment engaged in the same behavioral repertoire. However, the behavioral repertoire of these nursery pigs were not different over the 3-d trial (previously published worked by Johnson et al., 2008) suggesting that the effects of this vaccination stressor and product were not long lasting

Pregnant and Nonpregnant Women in Cape Town, South Africa: Drug Use, Sexual Behavior, and the Need for Comprehensive Services

The multiple risks associated with methamphetamine use are of serious concern for women. These risks and consequences are magnified during pregnancy. This secondary analysis of a parent study compared 26 pregnant to 356 nonpregnant women in Cape Town, South Africa, on selected demographic, psychosocial, and HIV-risk domains to identify their treatment service needs. Proportionally, more pregnant than nonpregnant women are using methamphetamine, P = .01, although a very high rate of women used methamphetamine. Women reported similar monthly rates of sexual intercourse, but pregnant women were significantly less likely to report condom use, P < .0001, maintaining their risky behavior. Both groups reported elevated Center for Epidemiological Studies Depression Scale CES-D means, suggesting a need for depression treatment. Results demonstrate a pervasive need for women's comprehensive treatment, regardless of pregnancy status. Moreover, findings support the urgent need for women-focused and pregnancy-specific treatment services for methamphetamine use. Finally, a job-skills training/employment component focus is suggested

Pregnant and Nonpregnant Women in Cape Town, South Africa: Drug Use, Sexual Behavior, and the Need for Comprehensive Services

The multiple risks associated with methamphetamine use are of serious concern for women. These risks and consequences are magnified during pregnancy. This secondary analysis of a parent study compared 26 pregnant to 356 nonpregnant women in Cape Town, South Africa, on selected demographic, psychosocial, and HIV-risk domains to identify their treatment service needs. Proportionally, more pregnant than nonpregnant women are using methamphetamine, P = .01, although a very high rate of women used methamphetamine. Women reported similar monthly rates of sexual intercourse, but pregnant women were significantly less likely to report condom use, P < .0001, maintaining their risky behavior. Both groups reported elevated Center for Epidemiological Studies Depression Scale CES-D means, suggesting a need for depression treatment. Results demonstrate a pervasive need for women's comprehensive treatment, regardless of pregnancy status. Moreover, findings support the urgent need for women-focused and pregnancy-specific treatment services for methamphetamine use. Finally, a job-skills training/employment component focus is suggested

The Effect of Supplementing Dry Feed with a Nutritional Gel Product at the Time of Vaccination on Nursery Pig Maintenance Behaviors and Postures

Swine industry feed suppliers are continually striving to develop techniques and tools to reduce the additive stressors imposed on the weanling piglet, to increase advantageous behaviors (feeding and drinking) and to reduce aggressive interactions. One product on the market designed to ease the transition from a liquid diet (sow\u27s milk) to a dry ration is a gel-based feed supplement that was incorporated in this trial as a means to positively affect the aforementioned parameters. The trial was conducted in the spring of 2007. A total of 64 3-week old, crossbred pigs (4.2 kg) were received from a commercial farm and housed in Double L ® confinement nursery buildings. Four treatments were compared. Control groups (n = 4) were defined as unvaccinated and without supplemental gel at days 9 to 11. Treatment one (TRT 1 n = 4 groups) was provided supplemental gel at days 9 to 11 without vaccination. Treatment two (TRT 2; n = 4 groups) was vaccinated but did not receive supplemental gel at days 9 to 11. Treatment three (TRT 3; n = 4 groups) received supplemental gel at days 9 to 11 and were vaccinated. The group of four pigs housed together in a pen was considered the experimental unit for data analysis. Definitions for the behaviors and postures recorded and summarized for the trial included the following: Active was defined as standing, this included any upright postures. Inactive posture was defined as sitting or lying postures (both lateral and sternal). Time at drinker was defined as when an individual pig’s mouth was around the water nipple. Time at feeding stations was defined as the time when the individual pig’s head was inside the creep (that contained gel) or the three hole feeder (dry pelleted feed). There were no differences between treatments for active (P = 0.60), inactive (P = 0.99) or time at drinker (P = 0.37), respectively. There was a difference (P = 0.0085) between treatments for the percentage of time spent at the feeding stations with pigs receiving vaccine and no gel spending the least amount of time at the feeding stations compared to the other three treatment groups. Therefore, the availability of a gel product when pigs are vaccinated provided some benefit, as the time spent at the feeding station was higher compared to pigs that did not have access to the gel