MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse

Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4 × 20 mg/kg) or saline (n = 11-12/group). The right striatum was immunostained for tyrosine hydroxylase (TH). The left hemisphere was stained by Golgi Cox to quantify neuronal morphology in medium spiny neurons (MSNs) of the dorsolateral striatum. MPTP reduced TH, but there was no effect of castration and no interaction. For MSN dendritic morphology, MPTP decreased the highest branch order and increased spine density on 2nd-order dendrites. Castrated males had shorter 5th-order dendrites. However, there was no interaction between gonadal status and MPTP. Thus, castration and MPTP exert nonoverlapping effects on MSN morphology with castration acting on distal dendrites and MPTP acting proximally

Prospectus, February 18, 2009

https://spark.parkland.edu/prospectus_2009/1004/thumbnail.jp

The 2018 Martian Global Dust Storm over the South Polar Region studied with MEx/VMC

We study the 2018 Martian global dust storm (GDS 2018) over the Southern Polar Region using images obtained by the Visual Monitoring Camera (VMC) on board Mars Express (MEx) during June and July 2018. Dust penetrated into the polar cap region but never covered the cap completely, and its spatial distribution was nonhomogeneous and rapidly changing. However, we detected long but narrow aerosol curved arcs with a length of ~2,000–3,000 km traversing part of the cap and crossing the terminator into the nightside. Tracking discrete dust clouds allowed measurements of their motions that were toward the terminator with velocities up to 100 m/s. The images of the dust projected into the Martian limb show maximum altitudes of ~70 km but with large spatial and temporal variations. We discuss these results in the context of the predictions of a numerical model for dust storm scenario.This work has been supported by the Spanish project AYA2015-65041-P (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT-1366-19. J. H. B. was supported by ESA Contract 4000118461/16/ES/JD, Scientific Support for Mars Express Visual Monitoring Camera. We acknowledge support from the Faculty of the European Space Astronomy Centre (ESAC). VMC raw images used in this study can be accessed through VMC raw file gallery http://blogs.esa.int/ftp/. VMC raw and calibrated images will be available in ESA PSA in the near future. A list of observations used in this paper is provided in the supporting information. MCD database files are available in http://www-mars.lmd.jussieu.fr/mars.html

The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor

Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR

The Pseudomonas aeruginosa T6SS Delivers a Periplasmic Toxin that Disrupts Bacterial Cell Morphology.

The type VI secretion system (T6SS) is crucial in interbacterial competition and is a virulence determinant of many Gram-negative bacteria. Several T6SS effectors are covalently fused to secreted T6SS structural components such as the VgrG spike for delivery into target cells. In Pseudomonas aeruginosa, the VgrG2b effector was previously proposed to mediate bacterial internalization into eukaryotic cells. In this work, we find that the VgrG2b C-terminal domain (VgrG2bC-ter) elicits toxicity in the bacterial periplasm, counteracted by a cognate immunity protein. We resolve the structure of VgrG2bC-ter and confirm it is a member of the zinc-metallopeptidase family of enzymes. We show that this effector causes membrane blebbing at midcell, which suggests a distinct type of T6SS-mediated growth inhibition through interference with cell division, mimicking the impact of β-lactam antibiotics. Our study introduces a further effector family to the T6SS arsenal and demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

An Extremely Elongated Cloud Over Arsia Mons Volcano on Mars: I. Life Cycle

We report a previously unnoticed annually repeating phenomenon consisting of the daily formation of an extremely elongated cloud extending as far as 1,800 km westward from Arsia Mons. It takes place in the solar longitude (Ls) range of ∼220°–320°, around the Southern solstice. We study this Arsia Mons Elongated Cloud (AMEC) using images from different orbiters, including ESA Mars Express, NASA MAVEN, Viking 2, MRO, and ISRO Mars Orbiter Mission (MOM). We study the AMEC in detail in Martian year (MY) 34 in terms of local time and Ls and find that it exhibits a very rapid daily cycle: the cloud growth starts before sunrise on the western slope of the volcano, followed by a westward expansion that lasts 2.5 h with a velocity of around 170 m/s in the mesosphere (∼45 km over the areoid). The cloud formation then ceases, detaches from its formation point, and continues moving westward until it evaporates before the afternoon, when most sun-synchronous orbiters make observations. Moreover, we comparatively study observations from different years (i.e., MYs 29–34) in search of interannual variations and find that in MY33 the cloud exhibits lower activity, while in MY34 the beginning of its formation was delayed compared with other years, most likely due to the Global Dust Storm. This phenomenon takes place in a season known for the general lack of clouds on Mars. In this paper we focus on observations, and a theoretical interpretation will be the subject of a separate paper.This work has been supported by the Spanish project AYA2015-65041-P and PID2019-109467GB-I00 (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT-1366-19. JHB was supported by ESA Contract No. 4000118461/16/ES/JD, Scientific Support for Mars Express Visual Monitoring Camera. The Aula EspaZio Gela is supported by a grant from the Diputación Foral de Bizkaia (BFA). We acknowledge support from the Faculty of the European Space Astronomy Center (ESAC). Special thanks are due to the Mars Express Science Ground Segment and Flight Control Team at ESAC and ESOC. The contributions by K.C and N.M.S were supported by NASA through the MAVEN project

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

Evaluation of Mental Health First Aid from the Perspective Of Workplace End UseRs—EMPOWER: protocol of cluster randomised trial phase

Background: Mental Health First Aid (MHFA) is a mental health intervention that teaches people how to identify, understand and help someone who may be experiencing a mental health issue. Reviews of the implementation of MHFA found between 68 and 88% of trained Mental Health First Aiders had used their skills when in contact with someone experiencing mental health difficulties. Reviews evaluating the impact of MHFA suggest positive outcomes. However, to date, there has been no systematic, rigorous evaluation of the impact of MHFA on recipients of the intervention, the organisations providing it and the cost-effectiveness of MHFA overall. This trial will evaluate the effectiveness and cost-effectiveness of MHFA. Methods: The study is a multi-centred, two-arm clustered randomised controlled trial. Organisations will be randomly allocated to the control or intervention (estimated sample size 800 recipients). The intervention is the standard MHFA intervention provided by Mental Health First Aid England (MHFAE). The control condition will be organisations having a brief consultation from MHFAE on promoting mental health and well-being in the workplace. The primary outcome is health seeking behaviour, measured using the Actual Help Seeking Questionnaire, at 6 months’ follow-up. Data collection will be undertaken at baseline (T0), post-intervention—up to 3 months (T1), at 6 months (T2), 12 months (T3) and 24 months (T4). The primary analysis will be conducted on those participants who receive MHFA, a per protocol analysis. Discussion: The study is the first to evaluate the effect of MHFA in the workplace on employees with direct and indirect experience of the intervention, when compared with usual practice. Being also the first to assess, systematically, the social impact of MHFA and investigate its cost-effectiveness adds to the originality of the study. The study promises to yield important data, as yet unknown, regarding the effectiveness, cost-effectiveness, implementation issues, and the sustainability of MHFA in the workplace