Molecular cloning and cellular expression of the cholesterol synthesizing enzymes during the prenatal development of the optic nerve in the dromedary camel (Camelus Dromedarius)

The Cholesterol-synthesizing proteins (HMGCS1 and HMGCS2) are mitochondrial enzymes that believed to catalyze the first reaction of ketogenesis, the process by which energy is provided from fats in the absence of carbohydrates. Typically, astrocytes developed from its progenitor cells in the embryonic optic nerve and enriched with HMGCS1 and 2. However, the detailed histomorphology of camel HMGCS1 and 2 remains to be clearly defined. Here, we investigated the changes that associate with astrocytes differentiation within the developing camel optic nerve. Firstly, we isolated cDNAs encoding HMGCS1 and 2 from the optic nerve. Then, we found that HMGCS1 shared high similarity to human, while HMGCS2 showed a lower similarity and was more diverse. Immunohistochemical studies revealed that distinct correlation of astrocytes differentiation with HMGCS1 and 2 expressions in the developing camel optic nerve. Both encoded proteins were localized throughout the cytoplasm, as well as the nuclei of the astrocytes. In addition, semi-quantitative PCR analysis and western analysis confirmed that both HMGCS1 and 2 were highly expressed in camel optic nerve as well as other tissue, but they were lower in both skeletal and heart muscles. Moreover, various stains such as Sudan black and florescence filipin stains were used to visualize the free cholesterol in the astrocytes, indicating the enzymatic activity of HMGCS1 and 2. Together, our study reported the first comprehensive investigation of the molecular cloning and cellular expression of HMGCS1 and 2 in the optic nerve of dromedary camel.     

Review of the Captain America Graphic Novel ‘TRUTH: Red,White and Black’ Focusing on Parallels with the Infamous USPHS Syphilis Study at Tuskegee

This review presents the first detailed presentation of the parallelism between the Tuskegee Syphilis Study and the Captain America graphic novel ‘TRUTH: Red, White and Black’, published as a graphic novel by Marvel Comics in 2004 as a paperback, and then in 2009 as a hardcover. First written, published and distributed monthly in 2003 as pre-sequel seven comic book series to tell the story of the origins of the WWII superhero Captain America. In 2003, Marvel Comics chose to tell a ‘very dark story’ to explain the origins of Captain America, a half century after the initial introduction of Captain America as a WWII action hero in 1940. By detailing—for the first time—nine parallel aspects between these two storylines, this review demonstrates how Marvel Comics brought the tragic Tuskegee Syphilis Study story into the popular press, thus reaching an audience far beyond traditional bioethics academicians. This review is intended to stimulate and guide classroom discussions on the ethical issues at the core of the infamous Tuskegee Syphilis Study allowing bioethical issues to be made more accessible to the general public, via school curriculums, by the use of graphic novels.     

Dexamethasone mediated downregulation of PGC-1α and visfatin regulates testosterone synthesis and antioxidant system in mouse testis

Dexamethasone, a synthetic glucocorticoid has been used as an immunosuppressive and anti-inflammatory and affects reproduction. It has been suggested that testicular steroidogenesis involves PGC-1α and visfatin as key regulators. Previous studies have shown that dexamethasone down-regulates PGC-1α and visfatin expression in muscle and mammary epithelial cells respectively. However, the effect of dexamethasone on testicular visfatin and PGC-1α expressions has not been investigated. The aims of the present study were to investigate the effect of dexamethasone, on the expression of PGC-1α, visfatin and antioxidant enzymes activities in mouse testis. The results of the present study showed that dexamethasone treatment significantly decreased the expression of visfatin and PGC-1α in mice testis, along with significant decreased in testicular antioxidant enzymes activates. Further, dexamethasone treatment also significantly increased the testicular lipid peroxidation and decreased testosterone synthesis. The dexamethasone induced changes in PGC-1α and visfatin in the testis were significantly correlated with changes in serum testosterone concentrations and antioxidant enzymes activities. Thus, dexamethasone induced testicular toxicity may involve the PGC-1α and visfatin as important molecules to exhibit its effects.     

Immunolocalization of VEGF/VEGFR system in human fetal vomeronasal organ during early development

The vomeronasal system (VNS) is an accessory olfactory structure present in most mammals adhibited to the detection of specific chemosignals implied in social and reproductive behavior. The VNS comprises the vomeronasal organ (VNO), vomeronasal nerve and accessory olfactory bulb. VNO is characterized by a neuroepithelium constituted by bipolar neurons and supporting and stem/progenitor cells. In humans, VNO is present during fetal life and is supposed to possess chemoreceptor activity and participate in gonadotropin-releasing hormone neuronal precursor migration toward the hypothalamus. Instead, the existence and functions of VNO in postnatal life is debated. Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been demonstrated to play fundamental roles in various neurogenic events. However, there are no data regarding the localization and possible function of VEGF/VEGFRs in human fetal VNO. Therefore, this study was conceived to investigate the expression of VEGF/VEGFRs in human VNO in an early developmental period (9–12 weeks of gestation), when this organ appears well structured. Coronal sections of maxillofacial specimens were subjected to peroxidase-based immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. Double immunofluorescence for VEGF, VEGFR-1 or VEGFR-2 and the neuronal marker protein gene product 9.5 (PGP 9.5) was also performed. VEGF expression was evident in the entire VNO epithelium, with particularly strong reactivity in the middle layer. Strongly VEGF-immunostained cells with aspect similar to bipolar neurons and/or their presumable precursors were detected in the middle and basal layers. Cells detaching from the basal epithelial layer and detached cell groups in the surrounding lamina propria showed moderate/strong VEGF expression. The strongest VEGFR-1 and VEGFR-2 expression was detected in the apical epithelial layer. Cells with aspect similar to bipolar neurons and/or their presumable precursors located in the middle and basal layers and the detaching/detached cells displayed a VEGFR-1 and VEGFR-2 reactivity similar to that of VEGF. The basal epithelial layer exhibited stronger staining for VEGFRs than for VEGF. Cells with morphology and VEGF/VEGFR expression similar to those of the detaching/detached cells were also detected in the middle and basal VNO epithelial layers. Double immunofluorescence using anti-PGP 9.5 antibodies demonstrated that most of the VEGF/VEGFR-immunoreactive cells were neuronal cells. Collectively, our findings suggest that during early fetal development the VEGF/VEGFR system might be involved in the presumptive VNO chemoreceptor activity and neuronal precursor migration.     

Black Light Smokers: How Nicotine Intake and Carcinogen Exposure Differ Across Various Biobehavioral Factors

ObjectiveThe study objective was to identify biobehavioral variables associated with greater intake of nicotine and a tobacco carcinogen among Black light smokers who smoke 1 to 10 cigarettes per day (CPD).MethodsWe analyzed baseline data collected from 426 Black light smokers enrolled in Kick It at Swope III (KIS III), a smoking cessation trial for Black smokers. We examined differences in concentrations of tobacco biomarkers, including urinary total nicotine equivalents (TNE) and total 4-(methylnitrosamino)-1-(3)pyridyl-1-butanonol (NNAL; a human carcinogen), across gender, age, plasma nicotine metabolite ratio (NMR), CPD, and measures of tobacco dependence, including time to first cigarette (TFC), using ANOVA.ResultsTobacco biomarker levels were significantly higher among those who smoked more CPD (6–10 vs 1–5 CPD) and those with greater reported physical dependence on tobacco. Concurrently, those who smoked 1–5 CPD smoked each cigarette more intensely than those who smoked 6–10 CPD. While we found no gender differences overall, among those who smoked 1–5 CPD, women had higher NNAL levels compared to men. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, was not significantly related to TNE or NNAL levels.ConclusionAmong Black Light smokers, higher cigarette consumption and greater physical dependence—but not rate of nicotine metabolism, menthol use, or socioeconomic status—were associated with greater toxicant exposure and thus a likely increased risk of tobacco-related diseases. The lack of data on light smokers, and specifically on Blacks, make this observation important given the disproportionate burden of lung cancer in this population.