Dopamine Neuron Stimulating Actions of a GDNF Propeptide

BACKGROUND: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed. METHODS AND FINDINGS: Here we present the neurobiological actions of dopamine neuron stimulating peptide-11 (DNSP-11), an 11-mer peptide from the proGDNF domain. In vitro, DNSP-11 supports the survival of fetal mesencephalic neurons, increasing both the number of surviving cells and neuritic outgrowth. In MN9D cells, DNSP-11 protects against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-induced cell death, significantly decreasing TUNEL-positive cells and levels of caspase-3 activity. In vivo, a single injection of DNSP-11 into the normal adult rat substantia nigra is taken up rapidly into neurons and increases resting levels of dopamine and its metabolites for up to 28 days. Of particular note, DNSP-11 significantly improves apomorphine-induced rotational behavior, and increases dopamine and dopamine metabolite tissue levels in the substantia nigra in a rat model of PD. Unlike GDNF, DNSP-11 was found to block staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing the release of cytochrome c from mitochondria. CONCLUSIONS: Collectively, these data support that DNSP-11 exhibits potent neurotrophic actions analogous to GDNF, making it a viable candidate for a PD therapeutic. However, it likely signals through pathways that do not directly involve the GFRalpha1 receptor

Addressing Gender Roles in Society through Chicago’s Womanhouse (1972)

Womanhouse was created as an exhibition artwork by Judy Chicago, Miriam Schapiro, and the students of the feminist art program at UCLA during the second wave feminist art movement. Created in an abandoned mansion, the installations were designed to represent how a woman’s life changes once she is married. To create the concept for each installation, the artists participated in consciousness-raising sessions that allowed them to voice their thoughts and feelings on a topic. The kitchen represented the nurturing side of women that were always caretakers and became mothers to their children. This work focused on essentialism, the celebration of the essence of being a woman. Essentialism worked towards the same goal that Womanhouse did, to come together and celebrate everything about being a woman. The entire exhibit was meant to show that when women become married, they are hopeful that they’ll become equals to their husband in the home, but instead, they become the housekeeper of the home and the caretaker of the children. I argue that Womanhouse was revolutionary because it used the consciousness-raising sessions to visualize the gender inequality that was happening to women every day

Acute Effects of a Glucose Energy Drink on the Attentional Blink

There has been a dramatic rise is the consumption of energy drinks (e.g., Red Bull) in the past decade, particularly among college students. However, there has been little laboratory research to examine the acute effects of energy drinks on cognitive performance. The purpose of this study was to investigate the effects of a glucose energy drink on an attentional blink task and on subjective measures of mental fatigue and stimulation. Attentional blink is a phenomenon observed in rapid serial visual presentation. When a subject is presented with a sequence of visual stimuli in rapid succession at the same spatial location on a computer screen, a participant will often fail to detect a second salient target occurring in succession if it is presented between 200–500 ms after the first one. In this study, participants were randomly assigned to one of six dose conditions (energy drink doses of 1.8 ml/kg, 3.6 ml/kg, 5.4 ml/kg, and 7.2 ml/kg, a decaffeinated placebo beverage and a no drink condition). Participants completed the cognitive task and subjective measures both at baseline and at 30 min. after dose administration. The results indicated that the energy drink increased feelings of stimulation and decreased feelings of mental fatigue in a dose-dependent fashion. By contrast, only the lower doses of energy drink improved accuracy on the attentional blink task. The results are consistent with findings of other stimulant drugs that improvements in cognitive performance are not linear but instead look like an inverted-U shaped function

Impact of medium chain fatty acid products and the replacement of commonly used antibiotics in swine feed

This study evaluated the effect of ZnO, carbadox, and medium chain fatty acids (MCFA) on weanling pig growth performance. A total of 360 pigs (DNA 400x200; 5.4 ±0.07kg bw) were used for a 35d growth experiment that were randomly assigned in a grouped completely randomized design. A total of 60 pens with approximately 6 pigs per pen were used. There were 10 pens as the experimental unit per treatment. Phase 1(d0 to 7) and Phase 2 (d7 to 21) included treatment diets and a common diet was fed during phase 3 (d21 to 42). Pigs were weighed weekly as well as feed disappearance and fecal scores collected. Individual treatment diets included: 1) control, 2) 3,000 ppm ZnO in phase 1 and 1,500 ppm ZnO in phase 2, 3) 50 g/ton carbadox, 4) 1% blend of C6:C8:C10, 5) 1% Feed Energy R2 (Feed Energy Corp, Des Moines IA), and 6) 1% FORMI GML (ADDCON, Bitterfeld-Wolfen, Germany). The overall treatment (d0 to 19) showed significantly greater (P0.05) Average Daily Feed Intake (ADFI) in overall treatment and likely accounted for increased ADG. Carbadox, C6:C8:C10, and FORMI showed similar ADG in overall treatment (P>0.05). Overall treatment (d0 to 35) showed ZnO diet ADG significantly higher than R2 (P0.05). Finally, pigs on ZnO and Carbadox showed growth improvement to those without treatment. MCFA diets show comparable growth to leading diets, but more research is necessary to conclude its ability to be a leading additive for the swine industry

A murine oral model for Mycobacterium avium subsp. paratuberculosis infection and immunomodulation with Lactobacillus casei ATCC 334

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) the causative agent of Johne’s disease, is one of the most serious infectious diseases in dairy cattle worldwide. Due to the chronic nature of this disease and no feasible control strategy, it is essential to have an efficient animal model which is representative of the natural route of infection as well as a viable treatment option. In this report, we evaluated the effect of different doses of M. paratuberculosis in their ability to colonize murine tissues following oral delivery and the ability of Lactobacillus casei ATCC 334, a nascent probiotic, to combat paratuberculosis. Oral inoculation of mice was able to establish paratuberculosis in a dose-dependent manner. Two consecutive doses of approximately 109 CFU per mouse resulted in a disseminated infection, whereas lower doses were not efficient to establish infection. All inoculated mice were colonized with M. paratuberculosis, maintained infection for up to 24 weeks post infection and generated immune responses that reflect M. paratuberculosis infection in cattle. Notably, oral administration of L. casei ATCC 334 did not reduce the level of M. paratuberculosis colonization in treated animals. Interestingly, cytokine responses and histology indicated a trend for the immunomodulation and reduction of pathology in animals receiving L. casei ATCC 334 treatment. Overall, a reproducible oral model of paratuberculosis in mice was established that could be used for future vaccine experiments. Although the L. casei ATCC 334 was not a promising candidate for controlling paratuberculosis, we established a protocol to screen other probiotic candidates

Whipping Up a New Flavor - Abstract

A 43-year old Indian man presented with two years of progressive gait imbalance, dysarthria, and cognitive decline. Neurological exam revealed supranuclear gaze palsy with impaired downgaze and loss of OKN quick phases, impaired horizontal pursuit, ideomotor apraxia, facial and arm dystonia, foot and toe chorea, hyperreflexia, retropulsion, and gait ataxia. Neuropsychological testing suggested subcortical dementia. Brain MRI revealed multiple nonenhancing, confluent, periventricular and juxtacortical T2 hyperintensities and severe atrophy with a hummingbird sign. A paraneoplastic panel, GAD antibodies, and NMDA antibodies were negative. CSF revealed normal white blood cell count, elevated protein (81), markedly elevated IgG index and synthesis, 15 oligoclonal bands, negative paraneoplastic panel, negative Whipple's DNA PCR, and negative CJD testing (negative tau quantity and ambiguous 14-3-3, not supporting the diagnosis of CJD). Body PET-CT and EEG were normal. Treatment with high dose steroids, IVIG, and plasmapheresis were ineffective. Brain biopsy showed a hypercellular cortex and white matter with spongiosis, gliosis, and diffuse inflammatory parenchymal and meningeal infiltrate. The cortex contained numerous inflammatory nodules with neuronophagia. Overall the features were nonspecific and most suggestive of an inflammatory meningoencephalitis, such as a viral infection, autoimmune disease, or paraneoplastic process. The patient continued to deteriorate and died from sepsis six years after disease onset. An autopsy was performed.SMcomplicationsofinfection

Whipping Up a New Flavor - Slides

A 43-year old Indian man presented with two years of progressive gait imbalance, dysarthria, and cognitive decline. Neurological exam revealed supranuclear gaze palsy with impaired downgaze and loss of OKN quick phases, impaired horizontal pursuit, ideomotor apraxia, facial and arm dystonia, foot and toe chorea, hyperreflexia, retropulsion, and gait ataxia. Neuropsychological testing suggested subcortical dementia. Brain MRI revealed multiple nonenhancing, confluent, periventricular and juxtacortical T2 hyperintensities and severe atrophy with a hummingbird sign. A paraneoplastic panel, GAD antibodies, and NMDA antibodies were negative. CSF revealed normal white blood cell count, elevated protein (81), markedly elevated IgG index and synthesis, 15 oligoclonal bands, negative paraneoplastic panel, negative Whipple's DNA PCR, and negative CJD testing (negative tau quantity and ambiguous 14-3-3, not supporting the diagnosis of CJD). Body PET-CT and EEG were normal. Treatment with high dose steroids, IVIG, and plasmapheresis were ineffective. Brain biopsy showed a hypercellular cortex and white matter with spongiosis, gliosis, and diffuse inflammatory parenchymal and meningeal infiltrate. The cortex contained numerous inflammatory nodules with neuronophagia. Overall the features were nonspecific and most suggestive of an inflammatory meningoencephalitis, such as a viral infection, autoimmune disease, or paraneoplastic process. The patient continued to deteriorate and died from sepsis six years after disease onset. An autopsy was performed.SMcomplicationsofinfection

Whipping Up a New Flavor - Video

A 43-year old Indian man presented with two years of progressive gait imbalance, dysarthria, and cognitive decline. Neurological exam revealed supranuclear gaze palsy with impaired downgaze and loss of OKN quick phases, impaired horizontal pursuit, ideomotor apraxia, facial and arm dystonia, foot and toe chorea, hyperreflexia, retropulsion, and gait ataxia. Neuropsychological testing suggested subcortical dementia. Brain MRI revealed multiple nonenhancing, confluent, periventricular and juxtacortical T2 hyperintensities and severe atrophy with a hummingbird sign. A paraneoplastic panel, GAD antibodies, and NMDA antibodies were negative. CSF revealed normal white blood cell count, elevated protein (81), markedly elevated IgG index and synthesis, 15 oligoclonal bands, negative paraneoplastic panel, negative Whipple's DNA PCR, and negative CJD testing (negative tau quantity and ambiguous 14-3-3, not supporting the diagnosis of CJD). Body PET-CT and EEG were normal. Treatment with high dose steroids, IVIG, and plasmapheresis were ineffective. Brain biopsy showed a hypercellular cortex and white matter with spongiosis, gliosis, and diffuse inflammatory parenchymal and meningeal infiltrate. The cortex contained numerous inflammatory nodules with neuronophagia. Overall the features were nonspecific and most suggestive of an inflammatory meningoencephalitis, such as a viral infection, autoimmune disease, or paraneoplastic process. The patient continued to deteriorate and died from sepsis six years after disease onset. An autopsy was performed.SMcomplicationsofinfection

Catchment to sea connection: impacts of terrestrial run-off on benthic ecosystems in American Samoa

Variation in water quality can directly affect the composition of benthic assemblages on coral reefs. Yet, few studies have directly quantified nutrient and suspended particulate matter (SPM) to examine their potential impacts on benthic community structure, especially around high oceanic islands. We assessed the spatio-temporal variation of nutrients and SPM across six sites in American Samoa over a 12-month period and used exploratory path analysis to relate dissolved inorganic nutrients, land use, and natural and anthropogenic drivers to benthic assemblages on adjacent shallow reefs. Multivariate analyses showed clear gradients in nutrient concentrations, sediment accumulation and composition, and benthic structure across watersheds. Instream nutrients and land uses positively influenced reef flat nutrient concentrations, while benthic assemblages were best predicted by wave exposure, runoff, stream phosphate and dissolved inorganic nitrogen loads. Identifying locality-specific drivers of water quality and benthic condition can support targeted management in American Samoa and in other high islands